Abstract
Background: The main proteases (Mpro) and Spike Proteins (SP) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) play a major role in viral infection development by producing several non-structural proteins (nsPs) and penetrating the host cells, respectively. In this study, the potential of in silico molecular docking-based drug repositioning approach was exploited for identifying the inhibitors of Mpro and SP of SARS-CoV-2.
Methods: A total of 196 compounds, including various US-FDA-approved drugs, vitamins, and their analogs, were docked with Mpro (PDB IDs: 6YB7 and 6Y84), and the top six ligands were further tested for ADME properties, followed by docking with SP (PDB IDs: 6LXT and 6W41).
Results: Out of 196 compounds, binding energy (DE) of Silybin B (6YB7: DE: -11.20 kcal/mol; 6Y84: DE: - 10.18 kcal/mol; 6LXT: DE: -10.47 kcal/mol; 6W41: DE: -10.96 kcal/mol) and Cianidanol (6YB7: DE: -8.85 kcal/mol; 6LXT: DE: -9.36 kcal/mol; 6Y84: DE: -10.02 kcal/mol; 6W41: DE: -9.52 kcal/mol) demonstrated better binding and ADME properties compared with the currently endeavored drugs like Hydroxychloroquine and Lopinavir. Additionally, Elliptinone, Diospyirin, SCHEMBL94263, and Fiboflavin have shown encouraging results. Fiboflavin, an immunity booster, was found to inhibit both the Mpro and spike protein of SARSCoV- 2. It was observed that amino acid residues MET6, ALA7, PHE8, PRO9, ASP295, GLY302, VAL303, and THR304 play significant roles in protein-ligand interactions through hydrogen bonds and Vander Waals forces.
Conclusion: Silybin B and Cianidanol showed excellent binding and ADME properties compared with the currently endeavored drugs and can be exploited as therapeutic options against SARS-CoV-2 infection after experimental validation and clinical trials.
Keywords: COVID-19, SARS-CoV-2, Mpro, spike protein, silybin B, cianidanol, fiboflavin.
Current Pharmaceutical Design
Title:Silybin B and Cianidanol Inhibit Mpro and Spike Protein of SARS-CoV-2: Evidence from in silico Molecular Docking Studies
Volume: 27 Issue: 32
Author(s): Rashi Srivastava, Shubham Tripathi, Sreepoorna Unni, Arif Hussain, Shafiul Haque, Nandita Dasgupta, Vineeta Singh*Bhartendu N. Mishra*
Affiliation:
- Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow- 226021, Uttar Pradesh,India
- Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow- 226021, Uttar Pradesh,India
Keywords: COVID-19, SARS-CoV-2, Mpro, spike protein, silybin B, cianidanol, fiboflavin.
Abstract:
Background: The main proteases (Mpro) and Spike Proteins (SP) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) play a major role in viral infection development by producing several non-structural proteins (nsPs) and penetrating the host cells, respectively. In this study, the potential of in silico molecular docking-based drug repositioning approach was exploited for identifying the inhibitors of Mpro and SP of SARS-CoV-2.
Methods: A total of 196 compounds, including various US-FDA-approved drugs, vitamins, and their analogs, were docked with Mpro (PDB IDs: 6YB7 and 6Y84), and the top six ligands were further tested for ADME properties, followed by docking with SP (PDB IDs: 6LXT and 6W41).
Results: Out of 196 compounds, binding energy (DE) of Silybin B (6YB7: DE: -11.20 kcal/mol; 6Y84: DE: - 10.18 kcal/mol; 6LXT: DE: -10.47 kcal/mol; 6W41: DE: -10.96 kcal/mol) and Cianidanol (6YB7: DE: -8.85 kcal/mol; 6LXT: DE: -9.36 kcal/mol; 6Y84: DE: -10.02 kcal/mol; 6W41: DE: -9.52 kcal/mol) demonstrated better binding and ADME properties compared with the currently endeavored drugs like Hydroxychloroquine and Lopinavir. Additionally, Elliptinone, Diospyirin, SCHEMBL94263, and Fiboflavin have shown encouraging results. Fiboflavin, an immunity booster, was found to inhibit both the Mpro and spike protein of SARSCoV- 2. It was observed that amino acid residues MET6, ALA7, PHE8, PRO9, ASP295, GLY302, VAL303, and THR304 play significant roles in protein-ligand interactions through hydrogen bonds and Vander Waals forces.
Conclusion: Silybin B and Cianidanol showed excellent binding and ADME properties compared with the currently endeavored drugs and can be exploited as therapeutic options against SARS-CoV-2 infection after experimental validation and clinical trials.
Export Options
About this article
Cite this article as:
Srivastava Rashi , Tripathi Shubham , Unni Sreepoorna , Hussain Arif , Haque Shafiul , Dasgupta Nandita , Singh Vineeta *, Mishra N. Bhartendu *, Silybin B and Cianidanol Inhibit Mpro and Spike Protein of SARS-CoV-2: Evidence from in silico Molecular Docking Studies, Current Pharmaceutical Design 2021; 27 (32) . https://dx.doi.org/10.2174/1381612826666201210122726
DOI https://dx.doi.org/10.2174/1381612826666201210122726 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Alogliptin: a Novel Molecule for Improving Glycemic Control in Type II Diabetes Mellitus
Current Diabetes Reviews Targeting HIV-1 gp41 in Close Proximity to the Membrane Using Antibody and Other Molecules
Current Topics in Medicinal Chemistry Pharmacogenomics and Personalized Use of Drugs
Current Topics in Medicinal Chemistry Plasmodium Dihydroorotate Dehydrogenase: A Promising Target for Novel Anti-Malarial Chemotherapy
Infectious Disorders - Drug Targets Arabidopsis thaliana- The Model Plant to Study Host-Pathogen Interactions
Current Drug Targets Impact of Drug Metabolism/Pharmacokinetics and its Relevance Considering Traditional Medicine-based Anti-COVID-19 Drug Research
Current Drug Metabolism The Impact of Crystallographic Data for the Development of Machine Learning Models to Predict Protein-Ligand Binding Affinity
Current Medicinal Chemistry Recent Advances in the Discovery and Development of Novel HIV-1 NNRTI Platforms (Part II): 2009-2013 Update#
Current Medicinal Chemistry From Dual Binding Site Acetylcholinesterase Inhibitors to Multi-Target-Directed Ligands (MTDLs): A Step Forward in the Treatment of Alzheimers Disease
Mini-Reviews in Medicinal Chemistry Possible Targets and Therapies of SARS-CoV-2 Infection
Mini-Reviews in Medicinal Chemistry Sterol 14α-Demethylase from Trypanosomatidae Parasites as a Promising Target for Designing New Antiparasitic Agents
Current Topics in Medicinal Chemistry Morelloflavone as Phytomedicine-An Ethnopharmacological Review on the Therapeutical Properties, Biological Efficacy and Pharmacological Activity
Anti-Infective Agents Chemistry and Biology of Indoles and Indazoles: A Mini-Review
Mini-Reviews in Medicinal Chemistry Viral Infection - A Cure for Type 1 Diabetes?
Current Medicinal Chemistry Maternal Sepsis 2010: Early Recognition and Aggressive Treatment with Early Goal Directed Therapy can Improve Maternal Outcomes
Current Women`s Health Reviews Interleukin-6 Blockers Improve Inflammation-Induced Lipid Metabolism Impairments but Induce Liver Fibrosis in Collagen-Induced Arthritis
Endocrine, Metabolic & Immune Disorders - Drug Targets Novel 4-Oxothienopyrimidinyl Propanoic Acid Derivatives as AMPActivated Protein Kinase (AMPK) Activators
Letters in Drug Design & Discovery A Systematic Review on Curcumin and Anti-<i>Plasmodium berghei</i> Effects
Current Drug Discovery Technologies Functional Antagonism between NF-κB and Nuclear Receptors: Implications in Carcinogenesis and Strategies for Optimal Cancer Chemopreventive Interventions
Current Cancer Drug Targets Remdesivir, A Potential Drug for COVID-19 Treatment: A New Hope
Coronaviruses