Details

Autor(en) / Beteiligte

• Bharadwaj, Shiv
• Azhar, Esam Ibraheem
• Kamal, Mohammad Amjad
• Bajrai, Leena Hussein
• Dubey, Amit
• Jha, Kanupriya
• Yadava, Umesh
• Kang, Sang Gu
• Dwivedi, Vivek Dhar

Titel

SARS-CoV-2 M pro inhibitors: identification of anti-SARS-CoV-2 M pro compounds from FDA approved drugs

Ist Teil von

• Journal of biomolecular structure & dynamics, 2022-04, Vol.40 (6), p.2769-2784

Ort / Verlag

England

Erscheinungsjahr

2022

Quelle

Taylor & Francis

Beschreibungen/Notizen

• Recent outbreak of COVID-19 pandemic caused by severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) has raised serious global concern for public health. The viral main 3-chymotrypsin-like cysteine protease (M ), known to control coronavirus replication and essential for viral life cycle, has been established as an essential drug discovery target for SARS-CoV-2. Herein, we employed computationally screening of Druglib database containing FDA approved drugs against active pocket of SARS-CoV-2 M using MTiopen screen web server, yields a total of 1051 FDA approved drugs with docking energy >-7 kcal/mol. The top 10 screened potential compounds against SARS-CoV-2 M were then studied by re-docking, binding affinity, intermolecular interaction, and complex stability 100 ns all atoms molecular dynamics (MD) simulation followed by post-simulation analysis, including end point binding free energy, essential dynamics, and residual correlation analysis against native crystal structure ligand N3 inhibitor. Based on comparative molecular simulation and interaction profiling of the screened drugs with SARS-CoV-2 M revealed R428 (-10.5 kcal/mol), Teniposide (-9.8 kcal/mol), VS-5584 (-9.4 kcal/mol), and Setileuton (-8.5 kcal/mol) with stronger stability and affinity than other drugs and N3 inhibitor; and hence, these drugs are advocated for further validation using enzyme inhibition and studies against SARS-CoV-2 infection.Communicated by Ramaswamy H. Sarma.