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Volume 24, 10 Issues, 2021
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Special Issue Submission
"Combinatorial Chemistry & High Throughput Screening is a pivotal journal in the field of drug discovery."
Norman R. Farnsworth
Univ. of Illinois at Chicago, USA
Herbal drug targets for COVID-19, Type 2 Diabetes, and cancer(s) and possible linkage with each other
Guest Editor(s): Mohammad Mobashir, Mohammad Amjad Kamal
Submit Abstract via Email
Novel Bioinformatics and Systems Biology approaches and techniques in Pharmaceutical and Biochemical Sciences
Guest Editor(s): Yudong Cai
Tentative Publication Date: December, 2016
In silico Methodologies Applied to Drug Discovery
Combinatorial Chemistry & High Throughput Screening, Volume 21, Number 3
Guest Editor(s): Luciana Scotti, Jahan Ghasemi, Marcus T. Scotti
I would like to thank you, Dr. Bijo Mathew and Bentham Science Publishers for providing help in all the steps of the publication process. It was a very good experience for me to work with Bentham Science Publishers due to your prompt replies to my queries. Thanks for everything.
48 Abstract Ahead of Print are available electronically
115 Articles Ahead of Print are available electronically
The biomedical society is entering the new era and big data and artificial intelligence since the launch of the Human Genome
Project (HGP) in the 1990s. The study mode of biomedical research is being shifted from the conventional observation
and empirical recording and sharing, to a new framework featured by mathematical and rational derivation. Artificial intelligence
provides ideal solution for simulation studies and full use of the available big data accumulated for last decades of biomedical
The thematic issue on Artificial Intelligence on High Throughput Data for Biomedical Research provides an excellent collection
of the latest research on bioinformatics and health informatics, particularly on the omics science, bioinformatics, and
health informatics. It also serves as a cutting-edge forum to bring together Interdisciplinary scientists from computer science,
biology, chemistry, medicine, mathematics and statistics.
Ten papers are selected by this thematic issue for publication. The study content covers the state-of-the-art research across
conventional medical research and the newest breakthrough in the new appearing biomedical research domains on both biomedicine
and artificial intelligence.
2. ARTICLES INCLUDED IN THE THEMATIC ISSUE
The paper “Analysis of miRNA-mRNA interaction network reveals gap junction beta 2 as a potential candidate gene involved
in psoriatic hearing loss pathogenesis” by Dinghong Wu et al. explore the psoriatic hearing loss pathogenesis by analyzing
the miRNA-mRNA network . The contribution by Pan et al. focused on the protective effects of Astragalus membranaceus
and Ligustrazine by observing the PKCδ/MARCKS pathway at the microvascular endothelial cell of oxygen-glucose
deprivation / reoxygenation by the brain injured rats . The paper entitled “Prognostic significance of hematopoietic-cell serglycin
for survival of hepatocellular carcinoma: a single-center retrospective study” by Yongwei Li et al. explores a new perspective
on the prognosis of liver cancer based on the level of hematopoietic-cell serglycin . Wanlu Zhang et al. introduced
popular blockchain method for medical image analysis .
In addition to the conventional domains, this thematic issue also demonstrates the integrative medicine aspects of biomedical
studies. Jun Liu et al. proposed their new idea of using herbal medicine to prevent deep venous thrombosis by promoting
blood circulation and removing blood stasis with AI methods . Tianshu Wang et al. uses the start-of-the-art deep convolutional
network to recognize the herbal component Crataegi Fructus . Ziping Li et al. proposed the application of data mining
to optimize the herbal formula for COVID-19 in their work “Analysis of Chinese herbal formulae recommended for COVID-19
in different schemes in China: A data mining Approach” . Hongxia Chen et al. introduced clinical study on shoulder-hand
syndrome as the complication of cerebral hemorrhage by herbal ointment . Shuo Jiang et al. demonstrated their clinical study
on acupuncture on depression . Finally, Yisheng Xu et al. performed a systematic review on the influence of diabetes to cuff
rotator treatment .
The preparation of this thematic issue is benefited from the collaboration of the editorial office of Combinatorial Chemistry
& High Throughput Screening and the guest editors. All manuscripts have undergone rigorous review and careful revision by
the authors. The guest editor would like to thank all the parties for their efforts on making this thematic a great success.
Molecular Chemo-Biological Effects is a mini-thematic issue publishing in Combinatorial Chemistry & High Throughput
Screening comprising 3 articles which studies the interactions of molecules and the biological effects which are produced as
shown in the three articles.
The List of articles:
− Acute inflammation and oxidative stress induced by lipopolysaccharide and the ameliorative effect of stingless bee
− Effect of visnagin on altered steroidogenesis and spermatogenesis, and testicular injury induced by the heavy metal
− Evaluation of insulin resistance induced brain tissue dysfunction in obese dams and their neonates: Role of ipriflavone
The Potential topics included in these articles are:
− Protection mechanism of synthetic compounds from combinatorial chemistry.
− Toxicity mechanism for toxic agent.
− Molecular interaction with synthetic chemical compounds.
− Genetic aberration and protection.
− Safety of using and addition of synthetic chemical and natural compounds and agents.
Methanol is an essential chemical for the synthesis of formaldehyde, MTBE, acetic acid, and a wide range of other products.
Low demand for MTBE, especially due to US decisions to eliminate it in gasoline, has led to a number of manufacturers around
the world seeking alternative uses for existing methanol units. In addition, the discovery of huge amounts of natural gas in the
world has led to the establishment of large industrial units for methanol production using existing technologies. One of the novel
and economical uses of methanol is the production of light olefins . Light olefins have many applications in the petrochemical
industry. Due to the growth of industry's need for light olefins and the lack of crude oil resources in the future, the
methanol to light olefins (MTO) using a non-oil source such as methanol is considered as an alternative method . Coal and
natural gas are abundant in nature, and today the methods of converting them to methanol are well known. Coal gasification or
steam reforming of natural gas to produce synthesis gas can lead to methanol production . Methanol can also be catalytically
converted to light olefins. Due to the use of crude methanol in the MTO process, if an MTO unit is constructed next to the
methanol production unit, its capital costs will also be decreased .
This special issue includes three main parts:
a) Synthesis and evaluation of suitable catalysts for the MTO process. Catalyst is the most important element in the
MTO process and directly affects the process yield and product selectivity. Therefore, the synthesis of this catalyst
with improved properties leads to the optimal MTO process and the production of high value-added products from
low-cost petroleum products such as synthesis gas and methanol .
b) Kinetic modeling for MTO reactions. The importance of the catalytic MTO process for petrochemical industries
confirms the need to develop kinetic modeling. Many studies have investigated the operating conditions, catalyst
synthesis, and its modification on the yield of light olefins. However, the mechanism and kinetic studies of this
process are still in the early stages. The kinetic study is one of the most important aspects of catalytic processes. It
helps simulate the reactor and estimates the distribution of products .
c) MTO process study. This section includes the evaluation of the effect of process conditions, along with the simulation
and optimization of the different types of reactors used in MTO process .
In the first article of the special issue, the hierarchical SAPO-34 / AlMCM-41 nanocomposite was synthesized using hydrothermal
and dry gel methods. Its performance in the MTO process was investigated by Rohollahi et al. . The second article
by Yazdanpanah et al. investigated the lifetime improvement of SAPO-34 nanocatalyst, which has a hierarchical structure using
clinoptilolite . In the Rimaz and Katal study as the third article, the positive effect of the dry gel synthesis method and the
use of carbon nanotube as a hard template to create a hierarchical structure on the performance of SAPO-34 catalyst in the
MTO process is discussed . Kianinia and Abdoli simulated the improved design of conversion of methanol to ethylene process
using Hysys software as the fourth article . In the fifth article by Aghaeinejad-Meybodi et al., the performance of a
membrane reactor in the MTO process was investigated using the 3-dimensional computational fluid dynamic method . In
the sixth article by Safaei and Taghizadeh, the mesoporosity was first introduced into a high silica ZSM-5 zeolite via an alkaline
treatment by NaOH solution with piperidine to decrease the diffusion limitation. Then the structure of zeolite was stabilized
by phosphorus modification to improve the acidic properties and enhance the catalyst stability .
In the seventh article, Sadeghpour et al. investigated the effect of two different methods of introducing nickel to the MFI
structure of ZSM-5 catalyst on its performance in the MTO process . In the eighth article by Aghamohammadi et al., the performance
of mono- and dual-template SAPO-34 catalysts in the MTO process were compared . In the final article, M.J.
Azarhoosh and A.R. Azarhoosh presented a 4-lumped dynamic kinetic model for the MTO process using a genetic algorithm .
We, the Guest Editors, would like to express our gratitude to the dear authors who contributed to this special issue.
Here, under this thematic issue titled “Contemporary Issues on Pharmaceutical Researches,” we sincerely invite you to contribute
to the current issue of the second volume of the journal “Combinatorial Chemistry & High Throughput Screening.”
The main aim of the issue is to present innovative and contemporary issues on pharmaceutical researches based on not only drug
analysis but also pharmaceutical technology, biotechnology, bioassays, medicinal chemistry, forensic chemistry, microbiology, pharmaceutical
chemistry, pharmacology, clinical pharmacy, biochemistry, natural, food and herbal products, drug toxicity research, and
so on. This special issue will contribute to the different fields of chemistry since the recent developments in multidisciplinary fields
are important and continuous. This volume II of the thematic issue involves 7 research papers [1-7].
In the first research paper, the research of Yurtdas Kirimlioglu et al. is focused on developing nanosized and non-toxic Eudragit®
RL 100 and Kollidon® SR nanoparticles loaded with moxifloxacin hydrochloride for its prolonged release for effective ocular delivery.
In vitro characterization analyses have shown that non-toxic, nano-sized, and cationic ERL-MOX2 formulation has the potential
to enhance ocular bioavailability. Moreover, Yıldırım et al. developed a simple and fast determination method of terbinafine, which is
an allylamine antifungal that is effective against many fungi, dermatophytes, and moulds present in human urine by dilute and shoot
HPLC-DAD using a core-shell column. The results of this study indicate that the combination of dilute and shoot approach and coreshell
column can be regarded as a practical application for the fast determination of terbinafine in the urine.
Furthermore, Levent et al. contributed to our special issue by a research article entitled “A novel and sensitive LC-MS/MS method for the
quantitation of ceftiofur in pharmaceutical preparations and milk samples.” The quantification of ceftiofur confirmed the applicability of this
method in routine in pharmaceutical preparations and treated-untreated milk samples. Celebier et al. studied electrochemical behavior and squarewave
stripping voltammetric determination of roflumilast in pharmaceutical dosage forms. This developed and validated SWSV method was
applied successfully for the determination of roflumilast in tablet dosage form to assess active roflumilast content.
In another study of our special issue, Özcan et al. suggested a novel HPLC method for simultaneous determination of methyl, ethyl, npropyl,
isopropyl, n-butyl, isobutyl, and benzyl paraben in pharmaceuticals and cosmetics. The proposed method was fully validated and
successfully applied to different pharmaceutical and cosmetic samples, including syrups, suspensions, oral sprays, and gels. This is the first
LC method, which is applicable both to pharmaceutical and cosmetic samples. Işık et al. also contributed to our special issue by their latest
study entitled “Electroanalytical analysis of guaifenesin on poly(acridine orange) modified glassy carbon electrode and its determination in
pharmaceuticals and serum samples.” The analytical applicability of the proposed method exhibited satisfying determination results for guaifenesin
from pharmaceutical dosage forms (syrup) and human serum samples without any pre-separation procedure.
In another research contribution, Agin et al. suggested voltammetric analysis of ephedrine in pharmaceutical dosage forms and
urine using poly (Nile blue A) modified glassy carbon electrode by cyclic voltammetry, differential pulse voltammetry, and square
wave voltammetry. The recovery studies on pharmaceutical dosage forms and urine showed that the proposed method exhibited good
selectivity, precision, and accuracy without any interference from inactive excipients.
In this special issue, we have collected several kinds of analyzing methods, investigated by different authors, to show the enrichment
of drug researches. Therefore, this thematic issue will be very useful for researchers who want to acquire knowledge on a broader
level. We would like to thank all of the authors one more time for their excellent contributions, the Editors of “Combinatorial
Chemistry & High Throughput Screening” for this kind invitation and having us as guest editors for this thematic issue and especially
the valuable assistance by the Editorial Manager, Mehjabeen Khan, and Assistant Manager Benish Amin, in the processing and finalization
of this special thematic issue.
Under this thematic issue entitled “Contemporary Issues on Pharmaceutical Researches” we sincerely invite you to meet
with the first part of the current issue of the journal “Combinatorial Chemistry & High Throughput Screening”.
The main aim of the issue is to present innovative and contemporary issues on pharmaceutical researches based on not only
drug analysis but also pharmaceutical technology, biotechnology, bioassays, medicinal chemistry, forensic chemistry, microbiology,
pharmaceutical chemistry, pharmacology, clinical pharmacy, biochemistry, natural, food and herbal products, drug toxicity
research and so on. This special issue will contribute to the different field of chemistry since the recent developments about multidisciplinary
issues are important and continuous. In part I of the thematic issue, there exist 10 research papers.
In the first research paper, a novel, accurate and sensitive reversed-phase high-performance liquid chromatography method
for the quantitative determination of voriconazole, luliconazole, clotrimazole, tioconazole, posaconazole, ketoconazole,
sertaconazole and terconazole in spiked human plasma was optimized and validated by Aboul-Enein et al. Electrochemical
behavior of rafoxanide on bare glassy carbon electrode was investigated and its determination in bovine milk was established
for the first time by adsorptive stripping method by Radi et al. The developed method was a sensitive, fast, cost-effective, highthroughput
and simple approach to determine rafoxanide in spiked bovine milk samples. Another high-performance liquid
chromatography study was presented by Dural. The aim of this study was to develop a validated simple, rapid and reliable highperformance
liquid chromatography method for the determination of dimethyl phthalate, diethyl phthalate, benzyl butyl
phthalate, di-n-butyl phthalate, and di(2-ethylhexyl) phthalate in cosmetic products and to investigate to these phthalate levels
in 48 cosmetic products marketing in Sivas, Turkey. In their research paper Asadpour-Zeynali et al. synthesized CoFe2O4 magnetic
nanoparticles by a facile co-precipitation synthesis method. Researchers developed a promising electrochemical sensor
based on CoFe2O4 magnetic nanoparticles modified glassy carbon electrode for electrochemical determination of methyldopa in
the presence of uric acid.
Additionally, Ozdemir et al. contributed to this thematic issue by a paper entitled The Association of CYP2D6*4 and POR*28
Polymorphisms on Mirtazapine Plasma Level in Subjects with Major Depressive Disorder and Anxiety Disorders. This study
aimed to assess the influence of CYP2D6*4 and POR*28 polymorphisms on MIR plasma levels in Turkish psychiatric patients.
The purpose of the study of Rebai et al. was to evaluate the association of this genetic polymorphism and the metabolomic profile
in Parkinson’s disease Tunisian patients, in order to identify effective biomarkers in the genetic differentiation.
Furthermore, in Roy et al. research, it aimed and developed sufficient strength of microparticle with a suitable concentration
of chitosan and non-ionic surfactants such as poloxamer-188 (pluronic). It also aimed to develop and study the effect of variables
for prepared microparticles utilizing in-silico screening methodology, such as reduced factorial design, followed by optimization.
Ozturk et al. contributed to this thematic issue by a paper entitled Design of Lamivudine Loaded Nanoparticles for Oral Application
by Nano Spray Drying Method: A New Approach to Use Antiretroviral Drug for Lung Cancer Treatment.
Lungu-Moscalu et al. proposed a new chromophore (Rhodamine B) for the assay of melatonin; this method succeeded to enlarge
the working concentration range, and to decrease the limit of determination comparing with the method that just used the
native fluorescence of melatonin. In the last contribution, Dindar et al. developed spectrophotometric and chromatographic methods
for the determination of Ephedrine, Naphazoline, Antazoline, and Chlorobutanol. All the analytical validation parameters for
the two suggested methods were achieved. Moreover, the results of the spectrophotometric and chromatographic methods were
compared with statistical data analysis, using student t-test and Fisher's statistical analysis with p < 0.05 as minimal level of significance.
No differences were found between the two methods and it was concluded that these estimated models are suitable.
In this volume, we collected several kinds of analyzing methods, investigated by different authors, to show the riches of
drug researches. Therefore, this thematic issue will be very useful for the researchers that wanted to have broad knowledge. We
want to thank all of the authors one more time for their excellent contributions, the Editors of “Combinatorial Chemistry &
High Throughput Screening” for this kind invitation to act us as guest editors for this thematic issue and especially the valuable
assistance by Editorial Manager, Mehjabeen Khan in the processing and finalization of this special theme issue.
Monoamine oxidase (MAO) catalyzes the oxidative deamination of
neurotransmitter monoamines and a variety of xenobiotic and dietary
amines . Two MAO isoforms, namely MAO-A and MAO-B, are
localized in the mitochondrial outer membrane . These two enzymes
show different substrate specificities; MAO-A prefers serotonin, whereas
MAO-B prefers phenylethylamine and benzylamine . Although most
marketed MAO drugs are long-lasting irreversible inhibitors, reversible
inhibitors have been developed to avoid protracted irreversible effects, for
example, moclobemide and safinamide, which are selective for MAO-A and MAO-B,
respectively, are used as an antidepressant and for the treatment of Parkinson’s disease (PD), respectively .
Acetylcholinesterase (AChE) is the main target in the palliative therapy of Alzheimer’s disease (AD), being present in
both central and peripheral nervous system and in muscular motor plaques, and it is responsible for the enzymatic
cleavage of neurotransmitter acetylcholine (ACh). Butyrylcholinesterase (BChE) present in the brain peripheral tissues
and in the serum, is up-regulated in advanced AD. Currently approved drugs for AD are the cholinesterase (ChE)
inhibitors, rivastigmine, galantamine, and donepezil . A number of reviews have been published on the ChE and MAO
inhibitors for establishing their roles on various neurodegenerative disorders [6-8]. The current thematic issue would
touch a specific class of both natural and synthetic derivatives as well as multi-targeting compounds.
The first article documented a detailed review of natural products and their potential inhibitory actions for MAO-B
and ChEs by Gulcan HO and Orhan IE. The study mainly highlighted the natural secondary metabolite structures and
their inhibitory profiles of both MAO-B and ChEs reported in the period of 2010-2019. The second perspective article by
the Mamun AA and Uddin MS highlighted the details of KDS2010, a potent, selective, and reversible MAO-B inhibitor
to abate the AD. The third article discussed the vital role of the enzymes, MAO and ChE, and discussed on the
pathophysiologic basis, focusing on drug research by Aksoz BE and Aksoz E. The fourth article by the Ramesh M and
Arunachalam M described the development in QSAR methodologies and its role in the design of newer monoamine
oxidase inhibitors. The fifth article by Parambi DGT gave the details of various types of MAO-B inhibitors for the
treatment of PD. The sixth article provided valuable information for the development of new class of various selective
MAO-A inhibitors for the treatment of depression and other anxiety disorders by Rehuman et al. The final perspective
article by Mathew B described the recent updates of chalcone moiety linked with the pharmacophores of flurbiprofen and
rivastigmine hybrids as selective ChE/MAO-B inhibitors for the prophylactic agents for AD.
Fourier Transform Infrared, Raman and NMR spectroscopic tools are potentially fruitful and
considered complementary and have been used for tracing conformational stabilities and
tautomer interchanges in addition to chemical/structural analysis. All are nondestructive
techniques for multi component sample analysis with good sensitivity and can be used for
monitoring/control industrial processes and environmental analysis. Since the 1990s,
computational chemistry and molecular modeling provide strong support for structural
elucidations/characterizations and spectral interpretations.
This special thematic issue entitled “Raman, Infrared and NMR Spectroscopy: Advances in
Structural, Conformational and Environmental Analysis” is proposed to highlight the critical
importance of these topics for ongoing progress in computational, conformational stability, inorganic and
environmental chemistry using IR, Raman and NMR spectroscopic and other techniques whenever appropriate. We
have compiled a collection of articles that address some of these research interests.
The content of this special issue reflects only four articles that have undergone the rigorous peer review phase of
the journal and whose authors have succeeded in meeting the criteria for numerous revisions to the original
submissions. These papers reflect a great deal of effort, thus conveying our gratitude for their hard work. We would
also like to thank the CCHTS editorial board for their moral support and a long list of anonymous reviewers for
insightful feedback and constructive critiques. While each of the following four papers is firmly focused on its own
potential, we have made an attempt to enforce a rough thematic structure and a logical flow in their order, inspired
by an interest in highlighting some of the methodological similarities and differences.
This issue begins with an article coauthored by the Guest editor, Professor Tarek A. Mohamed, which provides
an overview of using Quantum Mechanical (QM) calculations using DFT/B3LYP method compiled with Infrared,
Raman and UV-Visible Spectra of novel Schiff bases in addition to conformational analysis and structural
characterizations. The beginning of the article explains the significance and applications of Schiff bases,
accompanied by novel synthesis of two of them characterized by CHN elemental analysis, mid-infrared (400-4000
cm-1), Raman (100-4000 cm-1), 1H NMR and UV-Vis spectroscopic measurements. In addition, the hypothetically
proposed planar 2D and 3D structures were built against the azomethine lone-pair based on the orientations of both
CN and OH groups. Then, we performed complete geometry optimizations followed by frequency calculations.
Based on minimum energy and real wavenumber predictions, 3D non-planar form is preferred but imaginary
torsional vibrational frequencies were predicted for 2D planar (transition state). Reliable vibrational assignments for
observed infrared and Raman bands have been suggested, supported by NCA .
The second article, coauthored by Professor Ahmed Soliman, Cairo University on the synthesis and structural
identification assisted by QM calculations of new platinum(II) ternary complexes of formamidine and
pyrophosphate based on B3LYP method in addition to their in vitro cytotoxicity. The beginning of the article
examines the importance of Pt(II), Pt(IV) and pyrophosphate complexes in chemotherapy as potent cancer
treatments. The authors successfully synthesized diamagnetic square planar novel ternary platinum (II) complexes
with formamidine and pyrophosphate (1-4). Structures were evidenced by CHN, thermal analysis, magnetic
susceptibility in addition to infrared, UV-Visible and mass spectral measurements, thermal analyses. QM
calculations indicated a distorted square planar geometry where O-Pt-O, and N-Pt-N angles were ranged from
82.04° to 96.44°. HOMO’s and LUMO calculated energy ranges and the aforementioned measurements suggest
stable, neutral, non-hygroscopic complexes. Cytotoxicity with IC50 (μM) were also reported: 0.035-0.144 MCF-7
(breast cancer cell line), 0.042-0.187 HCT-116 (colon carcinoma cell line), and 0.063-0.168 HepG-2 (hepatocellular
cancer cell line), in which complex (4) has the best IC50 .
The third article, submitted by Ahmed Refaat, National Research Center, Cairo and his group focused on
B3LYP/6-31g(d,p) molecular modeling of sodium alginate (SA), cellulose and chitosan microspheres to be
applicable for the green route for the removal of Pb from aquatic environment. Molecular modeling and common
applications have been reviewed in the introduction. Cross-linked microspheres were prepared with different ratios.
SEM indicates homogeneous structures of cellulose while chitosan is deformed when blended with SA; FTIR
confirmed the presence of uniform matrices. Moreover, SA, cellulose, chitosan, SA/cellulose and SA/chitosan
model were subjected to HOMO, LUMO and electrostatic potential (ESP) B3LYP/6-31G(d,p) calculations. Crosslinked
SA removed Pb2+ from aquatic environments/waste water more efficiently rather than SA/cellulose and/or
SA/chitosan although their enhancement of antibacterial properties .
The final article is related to the applications of spinel ferrites and their nanoparticles in corrosion exposed by
M.M.B. El-Sabbah and his group; the corrosion of cobalt ferrite “CoFe2O4” thin film on Pt, stainless steel (SS), and
Cu substrates out from aqueous sulfate solution then anodized at room temperature. Corrosion studies were carried
out in acidic, neutral, and alkaline medium using open circuit potential and potentiodynamic polarization
measurements. The morphology and chemical structure of CoFe2O4 thin film on different substrates were
characterized using XRD, SEM and VSM. The authors recommend “CoFe2O4” thin film for safely use in neutral
and alkaline aqueous media for Pt and Cu substrates, but can be used unrestrictedly in case of SS substrate .
We hope the scientific community of the CCHTS can consider this special thematic issue an insightful and
valuable collection of articles.
The WHO defines that pathogenic microorganisms cause infectious
diseases, such as bacteria, viruses, parasites or fungi; the diseases can
spread, directly or indirectly, from one person to another. Zoonotic
diseases are infectious diseases of animals that can be transmitted to
humans. Pharmacological design applied to the discovery of
pharmacophores has expanded the use of CADD tools, from drug lead
identification to receptor-based screening, to identifying aspects in
active compounds (when located at a similar distances) that are both
common and essential. A pharmacophore’s importance is based on its
molecular recognition in biological systems, for example: in molecular ligand-receptor and DNA-protein couplings.
The in silico methods are based on an examination of the chemical structure of compounds, identifying features
responsible for specific biological activity, thus enabling the estimation of theoretical data and the validation of any
statistical model of a large set of compounds before they are synthesized, contributing significantly to accelerating
the design/discovery process and reducing the need for expensive lab work and clinical trials.
Theoretical studies using in silico methods have aided in the process of drug discovery. Technological advances
in the areas of structural characterization, computational science, and molecular biology have contributed to faster
development of new feasible molecules. Chemoinformatic studies show that a large fraction of compounds are
“drug-like” or at least, “lead-like” having structural and physicochemical properties that render them as potential
drugs or leads.
This thematic issue brings together theoretical studies of different methodologies, such as QSAR, docking,
chemometric tools, artificial intelligence and others applied to optimize the search for new drugs for the cure and
treatment of infectious diseases.
The parasitic protozoal infections leishmaniasis, human African trypanosomiasis, and Chagas disease are
neglected tropical diseases that pose serious health risks for much of the world’s population. Current treatment
options suffer from limitations, but plant-derived natural products may provide economically advantageous
therapeutic alternatives. Several germacranolide sesquiterpenoids have shown promising antiparasitic activities, but
the mechanisms of activity have not been clearly established. Arnston & Setzer, in their study entitled
“Macromolecular Targets of Antiparasitic Germacranolide Sesquiterpenoids: An In Silico Investigation” ,
used in-silico screening of known antiparasitic germacranolides against recognized protozoal protein targets in
order to provide insight into the molecular mechanisms of activity of natural products. Conformational analyses of
the germacranolides were carried out using density functional theory, followed by molecular docking. A total of 88
Leishmania protein structures, 86 T. brucei protein structures, and 50 T. cruzi protein structures were screened
against 27 antiparasitic germacranolides. The in silico screening has revealed which of the protein targets of
Leishmania spp., Trypanosoma brucei, and Trypanosoma cruzi are preferred by the sesquiterpenoid ligands.
The world is under the grasp of dangerous post-antibiotics and antimicrobials attack where common infections
may become untreatable, leading to premature deaths due to antimicrobial resistance (AMR). While an estimated
7,00,000 people die annually due to AMR, which is a public health threat to all communities in different parts of the
world regardless of their economic statuses. However, this threat is ample in low- and middle-income countries
which have lack of sanitation and health infrastructure. 68th World Health Assembly endorsed the Global Action
Plan on antimicrobial resistance. Consequently, many countries started drafting and committing to National Action
Plans against AMR. As strong as National Action Plans are in terms of prescribing rational use of antimicrobials,
infection control practices, and related public health measures, without strong health systems, these measures will
have a limited impact on AMR in developing countries. The major reason for AMR is due to microbial quorum
sensing (QS) that may be durable for the microbial community to generate inter-communication and virulence
effects via quorum sensing mechanisms. Global stewardship to combat antimicrobial resistance is to develop antiquorum
sensing compounds that can inhibit the biosynthetic pathway mediating different quorum sensing targets. It
may pave an effective attempt to minimize microbial quorum sensing mediated antimicrobial resistance. The review entitled “Recent breakthroughs in antimicrobial resistance induced quorum sensing biosynthetic pathway
mediated various targets and design of their inhibitors” of Kumar et al., describes various QS mediated
potential target enzymes, its connection to AMR, and to find out the corresponding QS biosynthetic target inhibitors
Escherichia coli various strains can cause alarmingly serious infections. Countries like Pakistan harbour the
class of bacteria with one of the highest rates of resistance, but very little has been done to explore their genetic
pool. The study of Haq et al., “Association of Virulence Genes with Antibiotic Resistance in Pakistani
Uropathogenic E. coli Isolates” , was designed to find out the frequency of virulence genes of Uropathogenic E.
coli and their association with antibiotic resistance along with the evolutionary adaptation of the selected gene
through phylogenetic tree. Isolates from 120 urinary tract infected patients were collected. Antibiotic sensitivity was
detected by the disk diffusion method and DNA extraction was done by the boiling lysis method followed by PCRbased
detection of virulence genes. Final results were analyzed using the chi-square test.
We, the Guest-Editors, would like to express our gratitude to the many authors who contributed to this special
issue, reporting investigations in various aspects of “In silico methodologies applied to anti-infections drug
Drug treatment is a patron saint of human health. It was conservatively estimated that the total revenue
of the worldwide pharmaceutical market exceeded 1.2 trillion U.S. dollars and the global expenditures in
the pharmaceutical research and development (R&D) totaled 179 billion U.S. dollars in the year of
Both the pharmaceutical market and the R&D expenditures are continuously increasing. In spite of
this, a large number of diseased individuals in the world were still untreated promptly without efficient
drugs every day, to die. This is mainly because drug discovery and development does not keep up with
disease evolution, especially viruses. It would take about 14 years and 800 millions of U.S. dollars to
bring a new drug of de novo design to the market by the traditional chemical synthesis [1, 2]. On the
other hand, diseases, especially cancers and viral flus are showing a globally explosive trend. The
number of diseased or infected individuals is remarkably increasing, and new types of disease including cancers are emerging.
For example, the severe acute respiratory syndrome (SARS) coronavirus outbreak in 2003, and the Middle East Respiratory
Syndrome (MERS) coronavirus in 2018 led to the infection of numerous individuals, some of whom died due to the lack of
efficitive drugs. The new coronavirus disease (COVID-19) outbreaking in December 2019 has infected more than 230,000
individuals, involving more than 100 countries as of March 20, 2020 (https://www.who.int/emergencies/diseases/novelcoronavirus-
2019/situation-reports), which was only three months past from the first report of the COVID-19 case. Therefore, it
is one of the challenging tasks that the global scientists and the engineers are jointly faced with how to improve the efficiency
of the pharmaceutical R&D. The advance in the genomics sequencing techniques allows in-depth peep into perspectives of
spatio-temporal activity of cell as well as metabolism of drugs in the cell [3-6]. Therefore, the next-generation sequencing databased
pharmaceutical R&D is becoming a new avenue of drug discovery and development. The computational drug
repositioning is a hot topic of the new pharmaceutical R&D. Compared with the traditional drug discovery and development,
the computational drug repositioning is of low side-effect risk, low investment and short R&D cycle. The past decades have
witnessed the vast achievement of the computational drug repositioning in the drug discovery and development [7-10]. The
thematic issue is intended to provide a forum to collect the latest advances related to computational drug repositioning.
Drug target interactions play a key role in the drug discovery and development. It is by targets which were directly
associated with a disease or regulated the downstream disease-causing genes that drugs impose its interference on the
pathological processes . Identifying drug targets is helpful not only to know the mechanism of drug action , but also to
identify potential adverse side-effects of drugs  and unexpected drug therapy (i.e., drug repositioning) [14, 15]. There are
many types of drug targets, such as G Protein-coupled receptor, Protein kinases, Enzymes, Ion channels, and Transporters. A
drug might simultaneously interact with multiple types of targets. Che et al.  proposed a new computational model to
identify drug target groups. They firstly constructed the drug-drug network by using the chemical-chemical interactions in the
STITCH database , then extracted drug feature by using the network embedding algorithm Mashup , and finally
classified drugs into target groups by using the trained support vector machine  (SVM) classifier. The method is beneficial
to evaluate the behavior of drugs.
Side-effects refer to adverse therapeutic phenotypes after drug treatment . The drug side-effects are closely associated
with drug discovery and development because most new drugs are tested or evaluated for side-effects prior to being brought to
the market . The reason why and the way how drug side-effect is generated are not clear so far. Zhou et al.  investigated
the associations between side-effect and drug substructure. Zhou et al.  built a relationship score between side-effect and
substructure using the chemical-chemical interactions in the STITCH database , which was tested for finding statistically
significant substructure given side-effect. The method enriches drug discovery and development in the evaluation of sideeffects.
Leukemia is a type of blood cancer, which clinically has four subtypes: acute lymphoblastic leukemia, chronic myelogenous
leukemia, acute myeloid leukemia and chronic lymphocytic leukemia [23, 24]. Lu et al.  presented a computational model
to investigate biochemical mechanisms of drugs related to four types of leukemia. The gene ontology (GO) terms  and
Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways  were firstly used to represent leukemia drugs. The
minimum redundancy maximum relevance algorithm  was then used to rank GO terms and KEGG pathways from most to
least relating leukemia drugs. The method would help discriminate biochemical mechanism of four types of leukemia drugs and
are helpful for discovery and development of new leukemia drugs.
Lysine malonylation is a type of protein post-translational modification (PTM), which refers to a process of malonyl group’
covalently modifying the ε-amine group of lysine residue . The PTMs might regulate pathological process of diseases and
thus, are feasible to become therapeutic targets of drug treatment . For example, the malonylation is responsible for type 2
diabetes . Therefore, identifying malonylation sites is crucial to drug design of type 2 diabetes. Wang et al.  presented a machine learning-based method for predicting malonylation sites. In this method, 941 features were used to represent
conservation, amino acid composition, physiochemical and biochemical properties and disorder of residues, and the random
forest  was used as a learning algorithm.
Retinal images provide an enriched view of such eye diseases as diabetic retinopathy, glaucoma and macular degeneration
[34, 35]. The analysis of retinal images can assist in detecting retinal abnormalities incurred potentially by cardiovascular and
retinal disorders. Zhang et al.  proposed a method based on texture features in analyzing and mining information from
retinal images. By quantifying and analyzing textural features of retinal images, they identified the retinal region and improved
the visualization of the retinal blood vessels. This method is helpful for visualizing and examining retinal blood vessels in
clinical practice, and is applicable to computer-aided visual examination of retinal images for the diagnosis of eye diseases.
Protecting proteins and DNA from oxidative stress , the antioxidant proteins are generally responsible for the prevention
of aging-related diseases, such as Alzheimer's disease  and Parkinson's disease . It is no doubt that the knowledge about
the antioxidant protein is helpful to design drugs of these diseases above. Xu et al.  presented a computational method to
predict the antioxidant protein. The amino acid compositions and 9-gap dipeptide compositions were used to encode protein,
the principal component analysis was for extracting informative feature and the SVM  for the classifier.
Genome of each living individual is unique and differs from that of any others, and the variations in the genome are closely
linked to phenotype including physical appearance, susceptibility to disease and response to drug treatments . The
variations of the genome might fall into different categories, such as single nucleotide polymorphisms (SNPs), insertion and
deletion (INDEL) polymorphisms . Li et al.  developed a package of software to simulate multi-variation of Cancer
genomes including SNPs, INDEL, and structural variations. The package is beneficial to detect cancer genome mutations.
Precision diagnosis and personalized therapy have been a dream for a long time, but now with the
technological development, they have become possible. We can early detect complex diseases not just
based on their phenotypes but also based on their molecular characteristics, such as genotype, gene
expression and metabolite. We see human body at an unprecedented resolution. The multi-omics data
helps us to better understand the human system and better intervene the dysfunction. We are at the best
time for medicinal research.
To accelerate precision diagnosis and personalized therapy, we organized this special issue to
introduce the latest developments.
He et al. collected the gene expression profiles from 265 tumor tissues of stage I patient from The Cancer Genome Atlas
(TCGA) databases. Using Cox regression model, they evaluated the association between gene expression and the overall survival
time of patients adjusting for gender and age at the initial pathologic diagnosis. 15 genes were significantly associated with overall
survival time of patients. Their results were helpful for prediction of the prognosis and personalized cancer management .
Xu et al. analyzed clinical data prospectively collected from 760 infertile patients visiting the second Affiliated Hospital and
Yuying Children’s Hospital of Wenzhou Medical University between June 1, 2016 and December 31, 2017. They found that
the fastest clinical pregnancy declining age was between 25 and 32, and female infertility type was evidenced as another key
predictive factor for the cumulative outcome of Assisted Reproductive Techniques (ART) .
An et al. collected 100 patients with Autoimmune Hepatitis (AIH) and 100 healthy volunteers. The levels of IL-17, IL-6,
IL-21 and TNF-α in peripheral blood of all the subjects were detected by enzyme-linked immunosorbent assay and the
frequency of Th17 cells and Treg cells was detected by flow cytometry. They found that Th17 cell frequency and their related
factors IL-17 and TNF-α, were associated with the liver damage, which might be used to monitor AIH disease severity .
Chen et al. analyzed the miRNAs in normal and Non-Small Cell Lung Cancer (NSCLC) patients. They found that miR-330-
3p was significantly up-regulated in NSCLC cell lines and tissues and miRNA-205 was significantly down-regulated in
NSCLC cell lines and NSCLC tissues. miR-330-3p promoted cell invasion and metastasis in NSCLC probably by promoting
EMT and miR-205 could restrain NSCLC, which was likely, by suppressing EMT .
Kataria et al. investigated the synthesized compounds for their antioxidant and in vitro inhibition activity against the jack
bean urease enzyme. They also carried out molecular simulations to determine the complete interaction of the newly
synthesized compounds within the protein pocket. The lead molecules they identified may be useful in treatment of serious
pathogenic conditions caused by urease enzyme .
Zhao et al. constructed a deep learning model to diagnose lung adenocarcinoma. Compared to the traditional methods which
take a single gene as a feature, the relative difference between gene pairs was a higher order feature. Using high-order features
to build the model can avoid instability and make the prediction results more reliable .
Zhong et al. constructed a machine learning model that can effectively predict not only the risk of recurrence of lung cancer
patients, but also the survival of patients. Their model was tested on several datasets and all showed good performance .
Xu et al. reported a case of Intrahepatic Biliary Cystadenoma (IBC) located in caudate lobe and described a typical
procedure of misdiagnosing this disease. The experience and lessons of misdiagnosis in this case may help other clinicians in
the accurate diagnosis of the rare disease .
Shen et al. reported a rare case of pancreatic tumor with duodenal obstruction accompanied by obstructive symptoms, which
was finally confirmed by laparotomy. This case indicated that radical operation appeared to be the first-choice treatment for
patients with malignant duodenal obstruction .
This special issue covered disease detection, drug development and patient therapy. It illustrated the representative scenarios
in precision medicine and could be a good reference for physicians and researchers.
With the development of Next Generation Sequencing (NSG) technologies and advanced deep learning
methods, precision medicine has become actionable. Many diseases can be detected much earlier than traditional
diagnosis methods. Based on patients’ molecular fingerprint, a personalized treatment can be formulated. Big
advances have been achieved, such as the inhibitors of PD-1 (programmed cell death protein 1) approved by the
FDA which can treat various cancers based on patients’ microsatellite instability (MSI).
To facilitate precision medicine, efforts from different areas are needed. In this special issue, we included the
latest precision medicine applications in different areas.
Zhang et al. investigated whether laparoscopic resection is non-inferior to open resection in treatment
outcomes of rectal cancer after neo-adjuvant chemo-radiotherapy. A total of 6 trials were analyzed and they found
that laparoscopic surgery correlated with a longer operative time but a shorter hospital stays, without superior advantages in short-term
survival rates or oncologic efficiency for locally treating advanced rectal cancer after neoadjuvant chemo-radiotherapy .
Huang et al. analyzed twenty-nine randomized control trials (RCTs) which included 1061 patients in the invasive-noninvasive sequential
ventilation group (In-non group) and 1074 patients in the invasive ventilation group (In group). Their results demonstrated that the application
of noninvasive sequential ventilation after invasive ventilation at the pulmonary infection control window has a significant influence on
ventilator-associated pneumonia (VAP) incidence, mortality and length of stay in the ICU .
Hu et al. compared the efficacy and safety of robot-assisted thoracic surgery (RATS) lobectomy versus video-assisted thoracic surgery
(VATS) for lobectomy in patients with non-small cell lung cancer (NSCLC). They discovered that RATS resulted in better mortality as
compared with VATS. But RATS seemed to have longer operative time and higher hospital costs .
Dai et al. analyzed 1186 lower rectal cancer patients from 10 studies, which included 646 laparoscopic and 540 open surgery patients.
They compared the surgical outcomes of laparoscopic surgery and open surgery. They found that both the surgeries had similar operation
time, but the use of the laparoscopic surgery was preferred due to less time in solid intake, short hospital stay time, limited blood loss and
lower complication rate .
Ye et al. collected the publications on comparison of video-assisted thoracoscopic surgery (VATS) versus open thoracotomy for nonsmall
cell lung cancer (NSCLC) patients from 2007 to 2017. A systematic literature search was conducted including 15 studies. Comparing
lobectomy with thoracotomy, thoracoscopic lobectomy was associated with a lower incidence of major complications, including lower rates
of prolonged pneumonia, atrial arrhythmias and renal failure. Lobectomy via VATS may be the preferred strategy for appropriately selected
NSCLC patients .
Liu et al. investigated the effect and mechanism of Hairy Calycosin on non-alcoholic fatty liver dieases (NAFLD) in rats. They
discovered that Hairy Calycosin can effectively control the lipid peroxidation in liver tissues of rats with NAFLD, reduce the levels of serum
TNF-α, IL-6, MDA and FFA, effectively improve the steatosis and inflammation of the liver tissue, and down-regulate the expression of
CYP2E1, thus inhibiting apoptosis of hepatocytes .
Lian et al. detected the expression of LncRNA MINCR and mRNA CDK2 in seventy-five surgically resected primary hepatocellular
carcinoma tissues and adjacent tissues. The expression of LncRNA MINCR and mRNA CDK2 in primary hepatocellular carcinoma tissues was
observed to be higher than that in adjacent tissues. They played a synergistic role in the invasion, and metastasis of hepatocarcinoma cells .
Ye et al. measured the MADD expression levels in normal human lung and human lung adenocarcinoma tissues using
immunohistochemistry. They found that MADD expression was significantly upregulated in lung adenocarcinoma tissue and it can promote
lung adenocarcinoma cell growth by inhibiting apoptosis .
The studies in this special issue showed how powerful the precision medicine was and how to apply precision medicine in clinical
practice. We hope it will inspire more doctors and scientists to perform precision medicine researches.
With the development of the high-throughput technologies, such as Next Generation Sequencing
(NSG) and deep learning analysis of images, precision medicine is no longer a dream and the early
diagnosis of complex diseases, such as cancers and pulmonary diseases, become possible. Not only
precision diagnosis but also precision treatment have achieved huge successes. The inhibitors of PD-1
(programmed cell death protein 1) has approved by the FDA can treat various cancers. The cancer
types are irrelevant, only the mutation pattern matters. It revolutionizes the treatment of diseases.
With all these exciting developments of early and accurate diagnosis using liquid biopsy and
personalized immunotherapy using targeted inhibitors, the underlying image analysis, sequencing
analysis and statistical analysis are the foundation. In this special issue, we included precision
medicine studies using various methods.
Yu et al. studied the association between vitamin D receptor (VDR) genetic polymorphism and lung cancer risk. Four
positions on VDR gene, namely ApaI (rs7975232), BsmI (rs1544410), FokI (rs10735810) and TaqI (rs731236), were
investigated. ApaI and FokI showed no associations while BsmI and TaqI were associated with lung cancer risk .
Ru et al. evaluated the efficacy and toxicity of anti-PD1 to chemotherapy in patients with non-small-cell lung cancer.
Among patients with advanced NSCLC, were observed greater survival benefit, with a favorable safety profile with anti-PD1
than with docetaxel .
Ruan et al. evaluated the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based
chemotherapy as second-line systemic therapy in people with metastatic colorectal cancer (CRC). Their results suggest that the
addition of bevacizumab to the chemotherapy therapy could be an efficient and safe option for patients with metastatic
colorectal cancer as second-line treatment and without increasing the risk of adverse event .
Xu et al. reported the rate of adverse event after 1-year follow-up of coronary artery disease (CAD) patients who received
percutaneous interventions (PCI) treatment. The rates for target vessel failure (TVF), target vessel revascularization, target
lesion revascularization, myocardial infarction and major adverse cardiac events were 8.5%, 4.1%, 4.2%, 2.0%, 8.7%,
respectively. The results were useful for post PCI treatment adverse event prevention .
Guo et al. screened genes that were significantly associated with drug resistance of lung cancer patients. They constructed a
diagnostic classification model using the expression level of five genes as the feature and the prediction accuracy reached 85%
Yuan et al. enrolled 120 children who were hospitalized in The First Hospital of Huzhou between January and December
2016 for respiratory tract infection due to M. pneumoniae. Nearly 90% of the resistant M. pneumoniae strains showed A to G
substitution at position 2063 of the 23S rRNA gene .
Xu et al. evaluated the serum ORM1 level in the resistance of EGFR-TKI and optimized the cut off value of ORM1 for the
diagnosis of EGFR-TKI resistance. When compared to those before treatment, the AUC of serum ORM1 concentration was
0.880 ± 0.038 with sensitivity of 92.9% and specificity of 73.8% in the resistance group. The cutoff value of serum ORM1 was
1.778 μg/ml for advanced EGFR-positive LUAD and 1.723 μg/ml after resistance to EGFR-TKI .
Zhang et al. applied several advanced computational methods, such as minimum redundancy maximum relevance (mRMR),
incremental forward search (IFS) and random forest (RF) to investigate cereal hull color at metabolic level. A total of 158 key
metabolites were found to be useful in distinguishing white cereal hulls from colorful cereal hulls. Their results provided new
insights into the molecular basis of complex traits .
Wang et al. developed a new computational pipeline to identify the Driver Mutation-Differential Co-Expresison (DM-DCE)
modules based on dysfunctional networks across 11 TCGA cancers. Their study sheds light on both cancer-specific and crosscancer
characteristics systematically .
Cai et al. compared the modified transverse colostomy with conventional methods. The operation time of stoma
construction was 34±10 minutes for the conventional method and 28±7 minutes for the modified method (P= 0.009). Patients
with conventional transverse colostomy were remarkably more likely to experience parastoma hernia (P= 0.048) and stoma
prolapse (P= 0.038). Overall, the modified transverse colostomy is a safe and effective diverting technique .
Wang et al. proposed a novel network embedding method, which can extract topological features of each drug combination
from a drug network that was constructed using chemical-chemical interaction information retrieved from STITCH. Their
support machine vector (SVM) classifier yielded a Matthews correlation coefficient (MCC) of 0.806 .
Zhu et al. analyzed the medical records and various data of patients with lymphocyte interstitial pneumonia (LIP). They
found that the diagnosis of lymphocyte interstitial pneumonia (LIP) with high-resolution CT can increase the clinical diagnosis
rate, reduce misdiagnosis and improve early detection .
Zhang et al. studied hemolymphangioma, a rare benign tumor. Early diagnosis of hemolymphangioma is difficult, because
its symptoms can be imperceptible for a long time. A case of 30-year-old hemolymphangioma woman patient with 2 years of
follow-up was reported and more understanding of hemolymphangioma was accumulated .
Hu et al. reported a rare case of esophageal cancer maxilla metastasis (ECMM) with the involvement of the right side of the
soft palate and maxillary sinus. They explored the possible mechanisms and predictors of esophageal cancer metastasis .
With these studies, we hope that more and more people will realize the power of advanced analysis in precision medicine
and utilize these methods in their practice.
With the development of Next-Generation Sequencing (NGS) and high throughput omics technologies, the whole picture of
complex diseases and biochemical processes can be revealed. But analyzing these big data and integrating various omics data
are a great challenge for pharmacologists and biologists. Take the TARGET (Therapeutically Applicable Research to Generate
Effective Treatments) project as an example, it provides a comprehensive genomic big data of childhood cancers, including
Acute lymphoblastic leukemia (ALL), Acute myeloid leukemia (AML), Kidney Tumors, Neuroblastoma (NBL) and
Osteosarcoma (OS). It is very difficult to determine the key molecular changes that drive tumorgenesis from millions of
transcriptome profiling, nucleotide variation, copy number variation and clinical data.
Meanwhile, the development of Artificial Intelligence (AI) technologies, such as deep learning methods, is also rapid.
Unfortunatly, the AI scientists who focus on machine learning and graph theory, are not familiar with the biological context of
the great challenges the pharmacologists and biologists are facing. IBM Watson is a good start for introducing AI to analyze
clinical information and medical literature. But we need more and more such inter-discipline studies or projects to overcome
the barrier between computational scientists and pharmacologists/biologists. Together, novel Bioinformatics and Systems
Biology methods and software may be developed to solve the big data analysis and the heterogeneous data integration problem.
Until then, the science community may find the cause of complex diseases and the compounds that may cure the diseases. In
this special issue, we demonstrated the application of novel bioinformatics and systems biology approaches and techniques in
pharmaceutical and biochemical sciences.
Li et al. established the prognostic model for gastric adenocarcinoma based on the six genes that were significantly
correlated with the survival time for patient death risk evaluation. ROC analysis was conducted in the training and validation
datasets, and their AUROC values were 0.774 and 0.723, respectively.
Chen et al. proposed a prediction model that used the extreme learning machine (ELM) algorithm as the prediction engine
to identify nitrated tyrosine residues. This model produced satisfactory results on the training dataset with a Matthew's
correlation coefficient of 0.757. The model was also evaluated by an independent test dataset that contained only positive
samples, yielding a sensitivity of 0.938.
Liu H et al. provided a modified mathematical model of tumor growth with two time delay effects that involve the
interaction between host cells, tumor cells and effector cells in order to understand the dynamic behavior of tumor growth. In
their model, biological relevance was explained and found to be different from the existing methods.
Liu T et al. proposed a novel integrated multi-label classifier with chemical-chemical interactions for prediction of chemical
toxicity effects. By testing the integrated classifiers on a dataset with chemicals and their toxicity effects on Accelrys Toxicity
database and non-toxic chemicals with their performance evaluated by jackknife test, an optimal integrated classifier was
selected as the proposed classifier, which provided quite high prediction accuracies and wide applications.
Wang S et al. presented a hybrid feature selection method mRMR-ICA which combines minimum redundancy maximum
relevance (mRMR) with imperialist competition algorithm (ICA) for cancer classification. The presented algorithm mRMRICA
utilizes mRMR to delete redundant genes and provide the small datasets for ICA. Experimental results including the
accuracy of cancer classification and the number of informative genes are improved for mRMR-ICA compared with the
original ICA and other evolutionary algorithms.
Jiang et al. proposed a new computational method for the identification of novel colorectal cancer (CRC)-associated genes.
The proposed method was based on existing proven CRC-associated genes, human protein–protein interaction networks, and
random walk with restart algorithm. Using the proposed method, they successfully identified 122 novel CRC-associated genes.
Wang C et al. developed an integrated model with five basic components and two time delays for the p53 network. Using
such time delays as the bifurcation parameter, the existence of Hopf bifurcation was given by analyzing the relevant
characteristic equations. Their results indicated that the transcriptional and translational delays can induce oscillation by
undergoing a super-critical Hopf bifurcation and the length of these delays can control the amplitude and period of the
These seven works proved that bioinformatics and systems biology approaches and techniques were very powerful in
pharmaceutical and biochemical sciences. We hope that more and more pharmacologists and biologists will try these
bioinformatics and systems biology methods in their studies.
The term in silico refers to the computational component silicium, indicating in silico methods that are used for experiments
performed by computers. This is a relatively new area, implemented in the mid-80s and until then, is rapidly developing and is
being widely used in industry and academy, especially in the field of drug design, which has contributed to the search for new
bioactive compounds for treating various diseases. The in silico methods are based on an examination of the chemical structure
of compounds, identifying features responsible for specific biological activity, thus enabling the estimation of theoretical data
and the validation of any statistical model of a large set of compounds before they are synthesized, contributing significantly to
accelerating the design/discovery process and reducing the need for expensive lab work and clinical trials [1-3].
Theoretical studies using in silico methods have aided in the process of drug discovery. Technological advances in the areas
of structural characterization, computational science, and molecular biology have contributed to the faster planning of new
feasible molecules. Chemoinformatic studies show that a large fraction of compounds are “drug-like” or at least, “lead-like”
having structural and physicochemical properties that render them as potential drugs or leads. This thematic issue will bring
together theoretical studies of different methodologies, such as QSAR, docking, chemometric tools, artificial intelligence and
other applied in order to optimize the search for new drugs for the cure and treatment of several diseases. Computational
screening of small molecule compounds against protein targets implicated in a disease of interest has been widely used to
discover inhibitors, potentially involving the identification of the successes in the interaction of the systematic chemical group
with a compound already known to inhibit a target, as in quantitative activity structure (QSARs), or by "fitting" a large
molecule into the database of compounds in the active site of the three-dimensional (3D) structure of a target protein based on
the calculated binding affinity of the molecule to the target. As the number of high-resolution protein structures and the
processing power of computers have increased exponentially in recent years, so the methods used in the computational database
to complement experiments with High-Throughput Screening (HTS) methods to improve efficiency and effectiveness of the
discovery of lead inhibitors. In addition, studies have shown that HTS success rates are increased to several folds when
compounds are prefiltered by computational screening [4, 5].
This issue brings reviews concerning various types of theoretical methods in drug discovery. Our manuscript, entitled
“Docking of Natural Products against Neurodegenerative Diseases: General Concepts”, discussed the health benefits that
products provide which have become a motive for the treatment studies of various diseases; among them, the neurodegenerative
diseases, like Alzheimer's, considered as the most common form of dementia, and Parkinson's, a major age-related
neurodegenerative disorder. Studies with natural products for neurodegenerative diseases (particularly through molecular
docking) search for, and then focus on those ligands which offer effective inhibition of the enzymes monoamine oxidase and
acetylcholinesterase. The review introduced the main concepts involved in docking studies with natural products: and also on
our group, which has conducted a docking study of natural products isolated from Tetrapterys mucronata for the inhibition of
The work of the Drs. Suroowan & Mahomoodally, “Herbal products for common auto-inflammatory disorders - Novel
approaches”, discussed novel therapeutic approaches that involve the use of nanoparticles loaded with Zingiber officinale
Roscoe extracts to specifically target the colon in irritable bowel disease. In silico approaches remain also a pertinent avenue to
unveil highly compatible herbal metabolites binding multiple targets involved in inflammation.
Synapsin II regulates neurotransmitter release from mature nerve terminals and plays an important role in the formation of
new nerve terminals. The associations of SYN II have been identified in various studies that are linked to the onset of
Schizophrenia. Schizophrenia is characterized by an abnormal behavior like obsession, dampening of emotions and auditory
hallucination. The review of Drs. Tahir & Sehgal, “Pharmacoinformatics and Molecular Docking studies reveal potential novel
compounds against Schizophrenia by target SYN II”, provided the structural insights which may be used for further
understating of the Schizophrenia therapeutic purposes by targeting SYN II and other inhibitors haunting.
Various currently available antimicrobial drugs are inadequate to control the infections and lead to various adverse drug
reactions. Efforts based on Computer-Aided Drug Design (CADD) can excavate a large number of databases to generate new,
potent hits and minimize the requirement of time as well as money for the discovery of newer antimicrobials. Pharmaceutical
sciences have also made development with advances in drug designing concepts. The present research article focuses on
studying various G-6-P synthase inhibitors from the literature cited molecular database. Docking and ADMET data of various
molecules were obtained by Schrodinger Glide and PreADMET software respectively. In the article of Dr. Lather et al., entitled
Virtual Screening of Novel Glucosamine-6-Phosphate Synthase Inhibitors, the results presented the efficacy of various
inhibitors towards enzyme G-6-P synthase. Docking scores, binding energy and ADMET data of various molecules showed
good inhibitory potential for G-6-P synthase as compared to standard antibiotics.
The manuscript of Dr. Paliwal and co-workers, “Pyrazole Schiff base hybrid as an anti-malarial agent: Synthesis, in vitro
screening and computational study”; provided evidence which implicate the pyrazole schiff base hybrids as potential prototypes
for the development of antimalarial agents.
The aim of the study by Dr. Rastija et al., entitled “QSAR analysis for antioxidant activity of dipicolinic acid derivatives”
was to derive robust and reliable QSAR models for clarification and prediction of antioxidant activity of 43 heterocyclic and
Schiff bases dipicolinic acid derivatives. Statistical performance of two different algorithms for splitting data into training and
test set (randomly and ranking method), as well as models obtained by two set of descriptors, was calculated by different
“In-silico studies of isolated phytoalkaloid against Lipoxygenase: study based on possible correlation” is the work of Dr.
Khan et al., which discussed various alkaloids of plant origin that have already shown lipoxygenase inhibition in-vitro with
possible correlation in in silico studies. Molecular docking studies were performed using MOE (Molecular Operating
Closing this issue, we can find the manuscript of Dr. Khattab and co-authors, entitled “Extraction, identification and
biological activities of saponins in sea cucumber Pearsonothuria graeffei”. The work aimed to separate, identify and test
various biological activities (anti-bacterial, antifungal, antileishmanial and anticancer properties) of saponins produced by the
holothurian Pearsonothuria graeffei from the Red Sea, Egypt.
We, the Guest-Editors, would like to express our gratitude to all the authors who contributed to this special issue, reporting
investigations on various aspects of in silico methodologies applied to drug discovery.
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