SARS-CoV-2 S Mutations: A Lesson from the Viral World to Understand How Human Furin Works.
Int J Mol Sci
; 24(5)2023 Mar 01.
Article
in English
| MEDLINE | ID: covidwho-2253944
ABSTRACT
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the etiological agent responsible for the worldwide pandemic and has now claimed millions of lives. The virus combines several unusual characteristics and an extraordinary ability to spread among humans. In particular, the dependence of the maturation of the envelope glycoprotein S from Furin enables the invasion and replication of the virus virtually within the entire body, since this cellular protease is ubiquitously expressed. Here, we analyzed the naturally occurring variation of the amino acids sequence around the cleavage site of S. We found that the virus grossly mutates preferentially at P positions, resulting in single residue replacements that associate with gain-of-function phenotypes in specific conditions. Interestingly, some combinations of amino acids are absent, despite the evidence supporting some cleavability of the respective synthetic surrogates. In any case, the polybasic signature is maintained and, as a consequence, Furin dependence is preserved. Thus, no escape variants to Furin are observed in the population. Overall, the SARS-CoV-2 system per se represents an outstanding example of the evolution of substrate-enzyme interaction, demonstrating a fast-tracked optimization of a protein stretch towards the Furin catalytic pocket. Ultimately, these data disclose important information for the development of drugs targeting Furin and Furin-dependent pathogens.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Furin
/
Proteolysis
/
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
/
COVID-19
Type of study:
Etiology study
Topics:
Variants
Limits:
Humans
Language:
English
Year:
2023
Document Type:
Article
Affiliation country:
Ijms24054791
Similar
MEDLINE
...
LILACS
LIS