In:
Current Pharmaceutical Biotechnology, Bentham Science Publishers Ltd., Vol. 22, No. 15 ( 2021-12), p. 2054-2070
Abstract:
In December 2019, an outbreak of a pneumonia-like illness, Corona virus
disease 2019 (COVID-19), originating from Wuhan, China, was linked to novel coronavirus, now termed SARS-CoV-2. Unfortunately, no effective drugs or vaccines have been reported
yet. The main protease (M PRO ) remains the most validated pharmacological target for the design
and discovery of inhibitors. Objective: The purpose of the study was to find a prospective natural scaffold as an inhibitor for
M PRO main protease in SARS-CoV-2 and compare it with repurposed antiviral drugs lopinavir
and nelfinavir. Methods: Natural compound libraries were screened for potential scaffold against M PRO main
protease. Molecular dynamics simulation, MM-GBSA and principal component analyses of enzyme- ligand complexes were carried out with the top-ranking hits and compared with the repurposed
antiviral drugs lopinavir and nelfinavir. Results: The structure-based virtual screening indicated phenylbenzopyrone of flavonoids as one
of the top-ranking scaffolds that have the potential to inhibit the main protease with the Oglycosidic form, performing better than the corresponding aglyconic form. Simulation studies
indicated that glycosidic form of flavonoid is a more suitable inhibitor with compounds rutin, procyanidin B6, baicalin and galloylquercetin, demonstrating high affinity and stability, and rutin,
emerging as one of the best candidate compounds. Interestingly, rutin was reported to have inhibitory activity against similar protease (3Cprotease of enterovirus A71) and implicated in
lung fibrosis. Conclusion: The present study on flavonoids, possessing a potential scaffold for inhibiting main
protease activity for all betacoronavirus is an attempt to provide new and safe drug leads within a reasonably short period.
Type of Medium:
Online Resource
ISSN:
1389-2010
DOI:
10.2174/1389201022666210127113027
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2021
SSG:
15,3
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