tetano
Editor, Senior Moderator
J Biomol Struct Dyn. 2020 May 5:1-19. doi: 10.1080/07391102.2020.1764868. [Epub ahead of print]
Potential Inhibitors of Coronavirus 3-Chymotrypsin-Like Protease (3CL[SUP]pro[/SUP]): An in silico screening of Alkaloids and Terpenoids from African medicinal plants.
Gyebi GA[SUP]1[/SUP], Ogunro OB[SUP]2[/SUP], Adegunloye AP[SUP]3[/SUP], Ogunyemi OM[SUP]1[/SUP], Afolabi SO[SUP]4[/SUP].
Author information
Abstract
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[SUP]pro[/SUP]), 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[SUP]pro[/SUP] using in silico approach.Bioactive alkaloids (62) and terpenoids (100) of plants native to Africa were docked to the 3CL[SUP]pro[/SUP] of the novel SARS-CoV-2. The top twenty alkaloids and terpenoids with high binding affinities to the SARS-CoV-2 3CL[SUP]pro[/SUP] were further docked to the 3CL[SUP]pro[/SUP] of SARS-CoV and MERS-CoV. The docking scores were compared with 3CL[SUP]pro[/SUP]-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[SUP]pro[/SUP], 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-Epibryonolic 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[SUP]pro[/SUP] 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.
KEYWORDS:
COVID-19; Coronavirus 3CLpro; Molecular docking; Natural product; SARS-CoV-2
PMID:32367767DOI:10.1080/07391102.2020.1764868
Potential Inhibitors of Coronavirus 3-Chymotrypsin-Like Protease (3CL[SUP]pro[/SUP]): An in silico screening of Alkaloids and Terpenoids from African medicinal plants.
Gyebi GA[SUP]1[/SUP], Ogunro OB[SUP]2[/SUP], Adegunloye AP[SUP]3[/SUP], Ogunyemi OM[SUP]1[/SUP], Afolabi SO[SUP]4[/SUP].
Author information
Abstract
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[SUP]pro[/SUP]), 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[SUP]pro[/SUP] using in silico approach.Bioactive alkaloids (62) and terpenoids (100) of plants native to Africa were docked to the 3CL[SUP]pro[/SUP] of the novel SARS-CoV-2. The top twenty alkaloids and terpenoids with high binding affinities to the SARS-CoV-2 3CL[SUP]pro[/SUP] were further docked to the 3CL[SUP]pro[/SUP] of SARS-CoV and MERS-CoV. The docking scores were compared with 3CL[SUP]pro[/SUP]-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[SUP]pro[/SUP], 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-Epibryonolic 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[SUP]pro[/SUP] 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.
KEYWORDS:
COVID-19; Coronavirus 3CLpro; Molecular docking; Natural product; SARS-CoV-2
PMID:32367767DOI:10.1080/07391102.2020.1764868