Affordable Access

deepdyve-link
Publisher Website

Peptide-like and small-molecule inhibitors against Covid-19.

Authors
  • Pant, Suyash1
  • Singh, Meenakshi2
  • Ravichandiran, V2
  • Murty, U S N3
  • Srivastava, Hemant Kumar3
  • 1 Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research Kolkata, Kolkata, West Bengal, India. , (India)
  • 2 Department of Natural Products, National Institute of Pharmaceutical Education and Research Kolkata, Kolkata, West Bengal, India. , (India)
  • 3 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research Guwahati, Guwahati, Assam, India. , (India)
Type
Published Article
Journal
Journal of biomolecular structure & dynamics
Publication Date
May 01, 2021
Volume
39
Issue
8
Pages
2904–2913
Identifiers
DOI: 10.1080/07391102.2020.1757510
PMID: 32306822
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Coronavirus disease strain (SARS-CoV-2) was discovered in 2019, and it is spreading very fast around the world causing the disease Covid-19. Currently, more than 1.6 million individuals are infected, and several thousand are dead across the globe because of Covid-19. Here, we utilized the in-silico approaches to identify possible protease inhibitors against SARS-CoV-2. Potential compounds were screened from the CHEMBL database, ZINC database, FDA approved drugs and molecules under clinical trials. Our study is based on 6Y2F and 6W63 co-crystallized structures available in the protein data bank (PDB). Seven hundred compounds from ZINC/CHEMBL databases and fourteen hundred compounds from drug-bank were selected based on positive interactions with the reported binding site. All the selected compounds were subjected to standard-precision (SP) and extra-precision (XP) mode of docking. Generated docked poses were carefully visualized for known interactions within the binding site. Molecular mechanics-generalized born surface area (MM-GBSA) calculations were performed to screen the best compounds based on docking scores and binding energy values. Molecular dynamics (MD) simulations were carried out on four selected compounds from the CHEMBL database to validate the stability and interactions. MD simulations were also performed on the PDB structure 6YF2F to understand the differences between screened molecules and co-crystallized ligand. We screened 300 potential compounds from various databases, and 66 potential compounds from FDA approved drugs. Cobicistat, ritonavir, lopinavir, and darunavir are in the top screened molecules from FDA approved drugs. The screened drugs and molecules may be helpful in fighting with SARS-CoV-2 after further studies.Communicated by Ramaswamy H. Sarma.

Report this publication

Statistics

Seen <100 times