Targeting allosteric pockets of SARS-CoV-2 main protease Mpro

• Published in: Journal of biomolecular structure & dynamics Vol. 40; no. 14; pp. 6603 - 6618
• Main Authors: Bhat, Zahoor Ahmad, Chitara, Dheeraj, Iqbal, Jawed, Sanjeev, B. S., Madhumalar, Arumugam
• Format: Journal Article
• Language: English
• Published: Taylor & Francis 22-09-2022
• Subjects: Allostery; combination therapy; COVID-19; Elbasvir; Glecaprevir; molecular dynamics simulations; pro; protease; Ritonavir; SARS-CoV-2
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2021.1891141

Repurposing of antivirals is an attractive therapeutic option for the treatment of COVID-19. Main protease (M
pro
)
, also called 3 C-like protease (3CL
pro
) is a key protease of SARS-CoV-2 involved in viral replication, and is a promising drug target for antivirals. A major challenge to test the efficacy of antivirals is the conformational plasticity of M
pro
and its future mutation prone flexibility. Suitable choice of drugs in catalytic and allosteric pockets appear to be essential for combination therapy. Current study, based on docking and extensive set of MD simulations, finds the combination of Elbasvir, Glecaprevir and Ritonavir to be a viable candidate for further experimental drug testing/pharmacophore design for M
pro
.
Communicated by Ramaswamy H. Sarma