tetano
Editor, Senior Moderator
Sci Rep
. 2020 Jul 27;10(1):12493.
doi: 10.1038/s41598-020-69337-9.
Identification of key interactions between SARS-CoV-2 main protease and inhibitor drug candidates
Ryunosuke Yoshino[SUP] 1 2 [/SUP], Nobuaki Yasuo[SUP] 3 [/SUP], Masakazu Sekijima[SUP] 4 5 [/SUP]
Affiliations
Abstract
The number of cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) has reached over 114,000. SARS-CoV-2 caused a pandemic in Wuhan, China, in December 2019 and is rapidly spreading globally. It has been reported that peptide-like anti-HIV-1 drugs are effective against SARS-CoV Main protease (M[SUP]pro[/SUP]). Due to the close phylogenetic relationship between SARS-CoV and SARS-CoV-2, their main proteases share many structural and functional features. Thus, these drugs are also regarded as potential drug candidates targeting SARS-CoV-2 M[SUP]pro[/SUP]. However, the mechanism of action of SARS-CoV-2 M[SUP]pro[/SUP] at the atomic-level is unknown. In the present study, we revealed key interactions between SARS-CoV-2 M[SUP]pro[/SUP] and three drug candidates by performing pharmacophore modeling and 1 μs molecular dynamics (MD) simulations. His41, Gly143, and Glu166 formed interactions with the functional groups that were common among peptide-like inhibitors in all MD simulations. These interactions are important targets for potential drugs against SARS-CoV-2 M[SUP]pro[/SUP].
. 2020 Jul 27;10(1):12493.
doi: 10.1038/s41598-020-69337-9.
Identification of key interactions between SARS-CoV-2 main protease and inhibitor drug candidates
Ryunosuke Yoshino[SUP] 1 2 [/SUP], Nobuaki Yasuo[SUP] 3 [/SUP], Masakazu Sekijima[SUP] 4 5 [/SUP]
Affiliations
- PMID: 32719454
- DOI: 10.1038/s41598-020-69337-9
Abstract
The number of cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) has reached over 114,000. SARS-CoV-2 caused a pandemic in Wuhan, China, in December 2019 and is rapidly spreading globally. It has been reported that peptide-like anti-HIV-1 drugs are effective against SARS-CoV Main protease (M[SUP]pro[/SUP]). Due to the close phylogenetic relationship between SARS-CoV and SARS-CoV-2, their main proteases share many structural and functional features. Thus, these drugs are also regarded as potential drug candidates targeting SARS-CoV-2 M[SUP]pro[/SUP]. However, the mechanism of action of SARS-CoV-2 M[SUP]pro[/SUP] at the atomic-level is unknown. In the present study, we revealed key interactions between SARS-CoV-2 M[SUP]pro[/SUP] and three drug candidates by performing pharmacophore modeling and 1 μs molecular dynamics (MD) simulations. His41, Gly143, and Glu166 formed interactions with the functional groups that were common among peptide-like inhibitors in all MD simulations. These interactions are important targets for potential drugs against SARS-CoV-2 M[SUP]pro[/SUP].