Computer-aided Evaluation of Anti-SARS-CoV-2 (3-chymotrypsin-like Protease and Transmembrane Protease Serine 2 Inhibitors) Activity of Cepharanthine: An In silico Approach

3-chymotrypsin-like protease (3CL(PRO)) is found in severe acute respiratory syndrome coronavirus (SARS CoV)-2, and transmembrane protease serine 2 (TMPRSS-2) in humans, both of them have a role in viral attachment and proliferation. 3CL(PRO) and TMPRSS-2 are the most vital target for the discovery of an anti-corona virus. One efficient approach used to screen potential active compounds against specific target proteins, such as 3CL(PRO) and TMPRSS-2, is molecular docking. Cepharanthine (CEP) exhibits antiviral activity in SARS-CoV at 9.5 mu g/mL IC50 level. This study aims to perform an in silico study on CEP against non-structural SARS-CoV-2 3CL(PRO) and host transmembrane protease serine 2 protein. Molecular docking studies were carried out using compounds against 3CL(PRO) and TMPRSS-2 proteins through Swiss model, Uniport, PROCHECK, Swiss PDB viewer, PyMol, and PyRx computerized software. CEP displayed strong binding interactions -8.5 and -7.4 Kcal/mol with the 3CL(PRO), and TMPRSS-2 proteins. In all cases, CEP showed better binding affinities than FDA-approved anti-corona virus drug (Camostat mesylate, CAM) is currently underused in COVID-19. CEP may be one of the potentials leads to fighting against SARS-CoV-2. Further in vivo studies should be required to support the findings of this study.

Automated summary

This study used molecular docking to investigate the binding affinity of Cepharanthine (CEP) with key proteins 3CL(PRO) and TMPRSS-2 in SARS-CoV-2.The results showed that CEP exhibited strong binding interactions with 3CL(PRO) and TMPRSS-2 proteins, suggesting its potential as a treatment for combating SARS-CoV-2. However, further in vivo studies are needed to validate these findings.