Computational guided identification of a citrus flavonoid as potential inhibitor of SARS-CoV-2 main protease
- PDF / 4,190,868 Bytes
- 15 Pages / 595.276 x 790.866 pts Page_size
- 100 Downloads / 198 Views
ORIGINAL ARTICLE
Computational guided identification of a citrus flavonoid as potential inhibitor of SARS‑CoV‑2 main protease Neelutpal Gogoi1 · Purvita Chowdhury2 · Ashis Kumar Goswami1 · Aparoop Das1,3 · Dipak Chetia1 · Bhaskarjyoti Gogoi4 Received: 13 August 2020 / Accepted: 20 October 2020 © Springer Nature Switzerland AG 2020
Abstract Although vaccine development is being undertaken at a breakneck speed, there is currently no effective antiviral drug for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19. Therefore, the present study aims to explore the possibilities offered by naturally available and abundant flavonoid compounds, as a prospective antiviral drug to combat the virus. A library of 44 citrus flavonoids was screened against the highly conserved Main Protease (Mpro) of SARS-CoV-2 using molecular docking. The compounds which showed better CDocker energy than the co-crystal inhibitor of Mpro were further revalidated by flexible docking within the active site; followed by assessment of drug likeness and toxicity parameters. The non-toxic compounds were further subjected to molecular dynamics simulation and predicted activity (IC50) using 3D-QSAR analysis. Subsequently, hydrogen bonds and dehydration analysis of the best compound were performed to assess the binding affinity to Mpro. It was observed that out of the 44 citrus flavonoids, five compounds showed lower binding energy with Mpro than the co-crystal ligand. Moreover, these compounds also formed H-bonds with two important catalytic residues His41 and Cys145 of the active sites of M pro. Three compounds which passed the drug likeness filter showed stable conformation during MD simulations. Among these, the lowest predicted IC50 value was observed for Taxifolin. Therefore, this study suggests that Taxifolin, could be a potential inhibitor against SARS-CoV-2 main protease and can be further analysed by in vitro and in vivo experiments for management of the ongoing pandemic. Graphic abstract
Keywords COVID-19 · SARS-CoV-2 · Flavonoids · Main protease · Molecular docking · Molecular dynamic Extended author information available on the last page of the article
13
Vol.:(0123456789)
Molecular Diversity
Introduction
Materials and methods
The COVID-19 pandemic caused by SARS-CoV-2 has emerged as a global threat affecting more than 17 million people globally [1]. The rapid and dynamic spread of the disease has baffled healthcare officials across the world. With 668,910 global mortality till date (6th August 2020), and with no effective treatment available, the quest for discovering a drug or vaccine against SARS-CoV-2 has accelerated [1]. In this crisis, a renewed interest in traditional phytomedicinal plants or natural compounds has garnered significant attention due to its medicinal properties, low toxicity and adverse effects [2, 3]. At present, antagonistic approach by blocking the integral replication system of SARS-CoV-2 is being considered as one of the effective antiviral therapeutic strategies. SAR
Data Loading...
