Microbial Bioinformatics is a rapidly evolving field of study that not only
encompasses health and food science areas, but also presents new opportunities
for advancement and innovation in engineering, manufacturing, and industrial
process improvements [1]. As new sequencing methods become more cost effective
and mobile, obtaining data for analysis is much less the obstacle than it once was [2-4]. The current resistance to widespread
comprehensive data inclusion and diverse applied implementation of findings is the storage and computing power to analyze and organize
raw data into usable and accessible formats. These hurdles will continue to be diminished with the improvement and application
of new and more sophisticated algorithms as the artificial intelligence and cloud computing eases the current technological infrastructure
burdens [5, 6].
The influx of omics data readily available for further analysis should be complemented by advancements in the structural modeling
in order to ensure the structure-function relationships derived are sound. The complementary effect of greater sequence and structural
refinement inputs serve to aid predictive elements as well as engineering of biomolecules, small molecule products, and in silico
systems with medicinal or industrial purposes. Primary sequences dictate later modifications and structure [7]. To properly assess activity
and function, the inclusive treatment of sequence, predicted modifications and corresponding structure, as well as the corresponding
activities of such products in a systems perspective is imperative (Computational systems biology).
Microbial systems have proven to be an invaluable simplistic model in systems biology, however when discussing medical microbiology
in the context of antimicrobial design microbial system inputs are not easily directly transferable to human systems. This aspect
may prove to be an advantage in development of antimicrobials that capitalize on these systematic differences in response to external
perturbation (A network property necessary for concentration robustness.) Longevity, spectrum of coverage, and reduced toxicity
of an antimicrobial treatment prove to be the difference between a theoretically good drug candidate, a later phase failure, and a
true blockbuster global health improvement dictating medication. Precision medicine and pharmacogenomics is becoming more mainstream,
as are more diverse and comprehensive microbial diagnostics becoming more affordable and accessible. The combination of
systems analysis, structure-function relationships of small molecule drug candidates, and experimental findings from high-throughput
screening and structural molecular dynamics validation methods provide improved stepping stones for drug discovery and development
with expanded success limiting toxicity and maximizing the therapeutic effect [8, 9].
The complementation of experimental and computational sciences is ever apparent. As technological advancements in the areas of
sequencing, data storage and acquisition, structural determinations, and systems biology arise, it is ever important that information is
integrated and otherwise built upon for future studies to maximize available resources [10]. Funding, allocation of researchers’ time,
and laboratory and computational resources need to be taken into account in order to maximize benefit while limiting redundancies
that contribute to the lag between major findings in academia and their clinical implementation internationally. The academia to clinical
availability factor of medicinally relevant small molecules will continue to improve, as will continually decreasing costs as more
successful, promising leads are distinguished from less favorable leads earlier on and with greater ease in the drug discovery process
[10, 11]. Distinguishing the winners from the losers earlier on in the drug discovery game will continue to contribute to less irrecoverable
costs and less overall risk endured by drug manufactures in order to bring a new drug to market in an attempt to stay ahead of
ever evolving microbial species presenting threats to human health globally, (Drug Delivery: Principles and Applications).
2. EXPLORING THE BIOLOGY AND STRUCTURAL ARCHITECTURE OF SORTASE ROLE ON BIOFILM FORMATION
IN GRAM POSITIVE PATHOGENS
Sortase enzymes are considered to be a powerful taught in all gram positive bacteria as it facilitates several functions including
adhesions, internalins, blood clotting, immune evasion factors and transporters for nutrients across the microbial cell wall envelope.
Due to its receptor availability, it is so called as universal drug target for gram positive pathogens. In present review Chandra Bose
Selvaraj et al. they firmly explained a role of sortase in the virulence of pathogens and were focused on determining the role of Sortase enzymes' involvement in anti-infective studies and also, on the mechanisms of surface protein anchoring to the cell wall envelope
by sortases, and highlight how it plays a strong role as drug target. Now it is considered as a promising target for the development
of new anti-infective drugs that aim to interfere with important Gram-positive virulence mechanisms, evasion of host defenses, and
biofilm formation. Many inhibitors of sortase have been identified using high-throughput or in silico screening of compound libraries,
and also have proved useful tools for probing the action model of the enzyme, several are also promising postulant for the development
into potent inhibitors [15, 16]. These research advances have greatly contributed to our knowledge of sortase cell wall anchoring,
providing a platform for therapeutic targeting and further study in industrial applications.
3. ANTIFUNGAL ACTIVITY, MODE OF ACTION, DOCKING PREDICTION AND ANTI-BIOFILM EFFECTS OF (+)-β-
PINENE ENANTIOMERS AGAINST CANDIDA SPP.
Candidiasis is a most common fungal infection caused by yeasts that belong to the genus Candida. The antimicrobial activities of
the isomers and enantiomers of pinene were evaluated against bacterial and fungal cells. In present study Ana Cláudia de Macêdo
Andrade et al. exfoliated an example by using biochemistry and in silco approaches through molecular docking simulation and the
effect on the biofilm reduction altogether to summarize, the mechanism of (+)-β-pinene most likely in interfering with the cell wall;
maintain molecular interaction with Delta-14-sterol reductase and, to a lesser extent, with 1, 3-β-glucan synthase; is effective in the
reduction of inhibition of the Candida biofilm [12-13]. (+)-β-pinene antifungal activity for effective to address candidiasis. Further,
toxicological bioassays and phase I and II clinical trials are now needed to investigate the promising antifungal activity of the (+)-β-
pinene as a potential candidate in the treatment of candidiasis which would be an innovative approach.
4. ANTIFUNGAL AND ANTIMICROBIAL PROPERTIES OF A PURIFIED PROTEASE INHIBITOR FROM MACROTYLOMA
UNIFLORUM SEEDS
Plant protease inhibitors (PPIs) are generally small proteins which play key roles in regulation of endogenous proteases and may
exhibit antifeedant, antimicrobial, antifungal, antitumor and cytokine inducing activities. Macrotyloma uniflorum is an unexploited
legume, which is rich in nutrients and promising therapeutic prospects. Manju Mohan et al. in the current study revealed the presence
of a serine protease at active site. Future studies in this direction have to be performed to completely elucidate the characteristic features
of Serine type protease inhibitor seed coat. The presence of protease inhibitor may be the cause for difficulty in human digestion
and it’s role in processing antifungal and antimicrobial properties which can be used effectively for its application as a potential sea
food preservative. An economical method to nullify the protease inhibitory activity which will increase the availability of a good protein
source at a cheaper cost, thereby, making it a much needed protein source to meet the middle and lower class necessities [14].
5. ANTI-HYERGLYCEMIC PROPERTIES OF A PURIFIED PROTEASE INHIBITOR FROM MACROTYLOMA UNIFLORUM
SEEDS
Hyperglycemia associated with diabetes mellitus is a major concern, which affects people with both type 1 and type 2 diabetes and
be controlled by diet management, exercise, anti- hypoglycemic agents, and insulin therapy. Manju Mohan et al. in these current study
evaluates anti-hyperglycemic activity of proteolytic enzymes purification which play central role in the biochemical mechanism of
germination and is intricately involved in many aspects of plant physiology and development [17]. The inhibitory effect of purified
protease on trypsin activity was characterized by enzyme kinetic study.To better understand the mechanism of protein mobilization,
undertaken the task of purifying and characterizing proteases, which occur transiently. The overall study revealed that MUPI is an
insulin sensitizer, and can be considered as a potent bioactive compound for diabetes. This innovative and challenging research will
open up new avenues which constitute an effective anti-hyperglycemic protein which may find application in treatment of diabetes
without evident toxic effects [18].
6. STRUCTURE-BASED VIRTUAL SCREENING FOR THE IDENTIFICATION OF HIGH AFFINITY SMALL MOLECULE
TOWARDS STAT3 FOR THE CLINICAL TREATMENT OF OSTEOSARCOMA
Signal transducer and activator of transcription 3 [STAT 3] plays major role in cell signalling pathways, but over expression of
this protein leads to osteosarcoma. STAT 3 is a latent cytoplasmic transcription factor which promote oncogenesis. STAT3 appears to
be an important mediator of chemo resistance in osteosarcoma. Ravina et al. in the present study focus on decreasing the over expression
of STAT3 protein by down regulating the pathway using chemical inhibitor to suppress STAT3 activity. Initial approach is made
via in silico method based on docking studies and pharmacophore profiling to identify best pre-established compound [19-27].
Moreover a compound Sorafenib found to be best established drug with effective affinity towards the targeted protein. Interestingly,
on further virtual screening investigation the total energy of virtual screened compound Pubchem CID-44815014 is better than the
entire set of pre-established inhibitors with preferable affinity and inhibitory action. The study foresee Sorafenib and 44815014 are
structurally cognate. Howbeit Sorafenib is efficient inhibitor, but novel compound 44815014 with great affinity towards STAT3 can
be emerge as an important drug in treatment of disease the future ahead. Although, this research will open up new horizons to deliberate
further utilization in in vivo and in vitro analysis. This research will contribute in determining the most effective chemical prospective
to fight against osteosarcoma.
7. STRUCTURE-BASED VIRTUAL SCREENING APPROACH FOR THE IDENTIFICATION OF POTENTIAL ANTICANCER
COMPOUNDS TARGETING CD20 FOR THE TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA
(CLL)
CD20 is a hydrophobic phosphoprotein commence on the surface of the human B lymphocyte cells, and play an essential role in
the proliferation and differentiation of b-cells giving rise to humeral immune response, emerged as a tantalizing therapeutic option for
the treatment of CLL. Kritika et al. in her study emphasis on determining drug which target chronic lymphocytic Leukemia (CLL) by
constrain the activity of CD-20.Author rationalize the interaction of the CD20 with its pre-established inhibitors for CD-20 and to render the new compound having high binding consonance against the target protein. By virtue of Insilco approaches which includes
depiction of targeted protein structure and validation by Ramachandran Plot [27-30]. Further docking studies carried out in addition
with pharmacophore and ADMET analysis for toxicity [31-32]. Withal, conspicuous from the docking studies of pre-established and
virtual screening [33-35] compound for CD-20 resulted in among all compounds top side with PubChem Id 36462 found to have good
affinity among all pre-established compound for desired protein receptor CD-20, whereas on compelling this study virtual screened
compound with PubChem CID-11753896 is inimitable for pharmacokinetics and it is preferable to pharmacological profile to prevent
CLL cancer. This innovative and challenging research will open up new avenues which constitute an effective protein CD-20 which
may find application in treatment of Chronic Lymphomatic Leukemia without evident toxic effects.