tetano
Editor, Senior Moderator
PLoS Comput Biol
. 2022 Nov 21;18(11):e1010667.
doi: 10.1371/journal.pcbi.1010667. Online ahead of print.
Amino acid variants of SARS-CoV-2 papain-like protease have impact on drug binding
Agata P Perlinska[SUP] 1 [/SUP], Adam Stasiulewicz[SUP] 1 2 [/SUP], Mai Lan Nguyen[SUP] 1 3 [/SUP], Karolina Swiderska[SUP] 4 [/SUP], Mikolaj Zmudzinski[SUP] 4 [/SUP], Alicja W Maksymiuk[SUP] 1 5 [/SUP], Marcin Drag[SUP] 4 [/SUP], Joanna I Sulkowska[SUP] 1 [/SUP]
Affiliations
Abstract
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused both a health and economic crisis around the world. Its papain-like protease (PLpro) is one of the protein targets utilized in designing new drugs that would aid vaccines in the fight against the virus. Although there are already several potential candidates for a good inhibitor of this protein, the degree of variability of the protein itself is not taken into account. As an RNA virus, SARS-CoV-2 can mutate to a high degree, but PLpro variability has not been studied to date. Based on sequence data available in databases, we analyzed the mutational potential of this protein. We focused on the effect of observed mutations on inhibitors' binding mode and their efficacy as well as protein's activity. Our analysis identifies five mutations that should be monitored and included in the drug design process: P247S, E263D-Y264H and T265A-Y268C.
. 2022 Nov 21;18(11):e1010667.
doi: 10.1371/journal.pcbi.1010667. Online ahead of print.
Amino acid variants of SARS-CoV-2 papain-like protease have impact on drug binding
Agata P Perlinska[SUP] 1 [/SUP], Adam Stasiulewicz[SUP] 1 2 [/SUP], Mai Lan Nguyen[SUP] 1 3 [/SUP], Karolina Swiderska[SUP] 4 [/SUP], Mikolaj Zmudzinski[SUP] 4 [/SUP], Alicja W Maksymiuk[SUP] 1 5 [/SUP], Marcin Drag[SUP] 4 [/SUP], Joanna I Sulkowska[SUP] 1 [/SUP]
Affiliations
- PMID: 36409737
- DOI: 10.1371/journal.pcbi.1010667
Abstract
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused both a health and economic crisis around the world. Its papain-like protease (PLpro) is one of the protein targets utilized in designing new drugs that would aid vaccines in the fight against the virus. Although there are already several potential candidates for a good inhibitor of this protein, the degree of variability of the protein itself is not taken into account. As an RNA virus, SARS-CoV-2 can mutate to a high degree, but PLpro variability has not been studied to date. Based on sequence data available in databases, we analyzed the mutational potential of this protein. We focused on the effect of observed mutations on inhibitors' binding mode and their efficacy as well as protein's activity. Our analysis identifies five mutations that should be monitored and included in the drug design process: P247S, E263D-Y264H and T265A-Y268C.