Jump to main content
Jump to site search

Issue 1, 2021
Previous Article Next Article

Identification of LASSBio-1945 as an inhibitor of SARS-CoV-2 main protease (MPRO) through in silico screening supported by molecular docking and a fragment-based pharmacophore model

Author affiliations

Abstract

In December 2019, an infectious disease was detected in Wuhan, China, caused by a new pathogenic coronavirus, named SARS-CoV-2. It spread very rapidly, and on March 11th of 2020, the outbreak was declared a pandemic by the World Health Organization. Currently, effective treatment options remain limited. SARS-CoV-2 enzyme main protease (MPRO) plays a pivotal role in the viral life cycle, making it a putative drug target. In order to identify suitable hits to develop inhibitors with adequate antiviral properties, we explored the LASSBio Chemical Library employing multiple strategies of virtual screening. A fragment-based pharmacophore model enabled the identification of key interactions involved in the molecular recognition at the catalytic site of MPRO, namely, with amino acid residues His41, His163 and Glu166. Docking-based virtual screening was performed, leading to the identification of LASSBio-1945 (9), a new hit of MPRO, presenting an IC50 = 15.97 μM. This compound, an 1,3-benzodioxolyl sulfonamide, represents an interesting starting point for subsequent hit-to-lead optimization steps and, to the best of our knowledge, a new distinct chemotype for MPRO inhibition.

Graphical abstract: Identification of LASSBio-1945 as an inhibitor of SARS-CoV-2 main protease (MPRO) through in silico screening supported by molecular docking and a fragment-based pharmacophore model

Back to tab navigation

Supplementary files

Article information


Submitted
07 Aug 2020
Accepted
11 Oct 2020
First published
02 Nov 2020

RSC Med. Chem., 2021,12, 110-119
Article type
Research Article

Identification of LASSBio-1945 as an inhibitor of SARS-CoV-2 main protease (MPRO) through in silico screening supported by molecular docking and a fragment-based pharmacophore model

L. S. Franco, R. C. Maia and E. J. Barreiro, RSC Med. Chem., 2021, 12, 110
DOI: 10.1039/D0MD00282H

Social activity

Search articles by author

Spotlight

Advertisements