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

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

Automated summary

The combination of Elbasvir, Glecaprevir, and Ritonavir has been identified as a potential candidate for further experimental drug testing and pharmacophore design for M-pro, according to a study utilizing docking and extensive molecular dynamics simulations. The conformational flexibility and future mutation proneness of M-pro pose significant challenges for evaluating the efficacy of antivirals. Selecting suitable drugs for catalytic and allosteric pockets is crucial for combination therapy.