Anthocyanin derivatives as potent inhibitors of SARS-CoV-2 main protease: An in-silico perspective of therapeutic targets against COVID-19 pandemic. Issue 16 (2nd November 2021)

• Record Type: Journal Article
• Authors: Fakhar, Zeynab; Faramarzi, Bahar; Pacifico, Severina; Faramarzi, Shadab
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 39:Issue 16(2021)
• Page Start: 6171
• Page End: 6183
• Publication Date: 2021-11-02
• Subjects: COVID 19 -- SARS-CoV-2 -- main protease -- anthocyanin derivatives -- pharmacophore modeling -- virtual screening -- docking workflow -- ADMET -- MD simulations; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2020.1801510
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: A new pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and become pandemic with thousands new deaths and infected cases globally. To treat the patients with coronavirus disease (COVID-19), currently no effective drug or vaccine is available. This necessity motivated us to explore potential lead compounds based natural products targeting main protease (M pro ) enzyme of SARS-CoV-2. The M pro enzyme plays a key role in mediating viral replication and transcription and thus being considered as an attractive drug target. Herein, comprehensive computational investigations were performed to identify new lead compounds against main protease enzyme. In this study, the candidate anthocyanin-derived compounds from PubChem database were filtered considering antiviral characteristics of anthocyanins. The structure-based pharmacophore modeling was developed based on the co-crystallized structure of the enzyme with its biological active inhibitor. The generated hypotheses were applied for virtual screening-based PHASE Screen Score. Docking based virtual screening work flow was used to generate hit compounds using HTVS, SP and XP based Glide Gscore. The obtained hit compounds were filtered using ADMET pharmacological and physicochemical properties screening. Molecular dynamics simulations were performed to explore the binding affinities of the considered compounds. Our study identified six best anthocyanin-derived natural compounds which could be used as promising lead compounds against main protease SARS-CoV-2 virus. GRAPHICAL ABSTRACT: UF0001 Communicated by Ramaswamy H. Sarma