Potential inhibitors of coronavirus 3-chymotrypsin-like protease (3CL^pro): an<i>in silico</i>screening of alkaloids and terpenoids from African medicinal plants

The novel coronavirus disease 2019 (COVID-19) caused by SARS-COV-2 has raised myriad of global concerns. There is currently no FDA approved antiviral strategy to alleviate the disease burden. The conserved 3-chymotrypsin-like protease (3CL^pro), which controls coronavirus replication is a promising drug target for combating the coronavirus infection. This study screens some African plants derived alkaloids and terpenoids as potential inhibitors of coronavirus 3CL^pro using <i>in silico</i> approach. Bioactive alkaloids (62) and terpenoids (100) of plants native to Africa were docked to the 3CL^pro of the novel SARS-CoV-2. The top twenty alkaloids and terpenoids with high binding affinities to the SARS-CoV-2 3CL^pro were further docked to the 3CL^pro of SARS-CoV and MERS-CoV. The docking scores were compared with 3CL^pro-referenced inhibitors (Lopinavir and Ritonavir). The top docked compounds were further subjected to ADEM/Tox and Lipinski filtering analyses for drug-likeness prediction analysis. This ligand-protein interaction study revealed that more than half of the top twenty alkaloids and terpenoids interacted favourably with the coronaviruses 3CL^pro, and had binding affinities that surpassed that of lopinavir and ritonavir. Also, a highly defined hit-list of seven compounds (10-Hydroxyusambarensine, Cryptoquindoline, 6-Oxoisoiguesterin, 22-Hydroxyhopan-3-one, Cryptospirolepine, Isoiguesterin and 20-<i>Epi</i>bryonolic acid) were identified. Furthermore, four non-toxic, druggable plant derived alkaloids (10-Hydroxyusambarensine, and Cryptoquindoline) and terpenoids (6-Oxoisoiguesterin and 22-Hydroxyhopan-3-one), that bind to the receptor-binding site and catalytic dyad of SARS-CoV-2 3CL^pro were identified from the predictive ADME/tox and Lipinski filter analysis. However, further experimental analyses are required for developing these possible leads into natural anti-COVID-19 therapeutic agents for combating the pandemic.Communicated by Ramaswamy H. Sarma.