Allosteric Hotspots in the Main Protease of SARS-CoV-2.
J Mol Biol
; 434(17): 167748, 2022 09 15.
Article
in English
| MEDLINE | ID: covidwho-1936840
ABSTRACT
Inhibiting the main protease of SARS-CoV-2 is of great interest in tackling the COVID-19 pandemic caused by the virus. Most efforts have been centred on inhibiting the binding site of the enzyme. However, considering allosteric sites, distant from the active or orthosteric site, broadens the search space for drug candidates and confers the advantages of allosteric drug targeting. Here, we report the allosteric communication pathways in the main protease dimer by using two novel fully atomistic graph-theoretical methods:
Bond-to-bond propensity, which has been previously successful in identifying allosteric sites in extensive benchmark data sets without a priori knowledge, and Markov transient analysis, which has previously aided in finding novel drug targets in catalytic protein families. Using statistical bootstrapping, we score the highest ranking sites against random sites at similar distances, and we identify four statistically significant putative allosteric sites as good candidates for alternative drug targeting.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Coronavirus 3C Proteases
Type of study:
Prognostic study
/
Randomized controlled trials
Language:
English
Journal:
J Mol Biol
Year:
2022
Document Type:
Article
Affiliation country:
J.jmb.2022.167748
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