Phenylbenzopyrone of Flavonoids as a Potential Scaffold to Prevent SARSCoV-2 Replication by Inhibiting its M^PRO Main Protease

Title:Phenylbenzopyrone of Flavonoids as a Potential Scaffold to Prevent SARSCoV-2 Replication by Inhibiting its M^PRO Main Protease

Volume: 22 Issue: 15

Author(s): Angamba M. Potshangbam*, Potshangbam Nongdam, A. Kiran Kumar and R.S. Rathore*

Affiliation:

• Department of Biotechnology, Manipur University, Manipur 795003,India

• Department of Bioinformatics, School of Earth, Biological and Environmental Sciences, Central University of South Bihar, Gaya, 824236,India

Keywords: Severe acute respiratory syndrome, SARS, SARS-CoV-2, COVID-19, Main protease M^PRO or 3CLpro, natural product, drug design, docking, molecular dynamics.

Abstract:

Background: 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.

Cite this article as:

Potshangbam M. Angamba *, Nongdam Potshangbam , Kumar Kiran A. and Rathore R.S. *, Phenylbenzopyrone of Flavonoids as a Potential Scaffold to Prevent SARSCoV-2 Replication by Inhibiting its M^PRO Main Protease, Current Pharmaceutical Biotechnology 2021; 22 (15) . https://dx.doi.org/10.2174/1389201022666210127113027