Amino acid variants of SARS-CoV-2 papain-like protease have impact on drug binding

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...

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Bibliographic Details
Published in:PLoS computational biology 2022-11, Vol.18 (11), p.e1010667
Main Authors: Perlinska, Agata P, Stasiulewicz, Adam, Nguyen, Mai Lan, Swiderska, Karolina, Zmudzinski, Mikolaj, Maksymiuk, Alicja W, Drag, Marcin, Sulkowska, Joanna I
Format: Article
Language:English
Subjects:
Amino Acids
Binding
Binding sites
Binding sites (Biochemistry)
Biology and life sciences
Coronavirus Papain-Like Proteases - genetics
Coronaviruses
COVID-19
COVID-19 vaccines
Design
Disease transmission
Drug development
Economic crisis
FDA approval
Genomes
Humans
Ligands
Medicine and health sciences
Mutation
Observations
Pandemics
Papain
Papain - chemistry
Papain - metabolism
Peptide Hydrolases - metabolism
Physical Sciences
Physiological aspects
Polypeptides
Protease
Proteases
Proteinase
Proteins
Research and Analysis Methods
RNA polymerase
RNA viruses
SARS-CoV-2 - genetics
Severe acute respiratory syndrome coronavirus 2
Vaccines
Viral diseases
Viruses
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Summary: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.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1010667