In Silico Evaluation of Cyclophilin Inhibitors as Potential Treatment for SARS-CoV-2.
Open Forum Infect Dis
; 8(6): ofab189, 2021 Jun.
Article
in English
| MEDLINE | ID: covidwho-1263681
ABSTRACT
BACKGROUND:
The advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provoked researchers to propose multiple antiviral strategies to improve patients' outcomes. Studies provide evidence that cyclosporine A (CsA) decreases SARS-CoV-2 replication in vitro and decreases mortality rates of coronavirus disease 2019 (COVID-19) patients. CsA binds cyclophilins, which isomerize prolines, affecting viral protein activity.METHODS:
We investigated the proline composition from various coronavirus proteomes to identify proteins that may critically rely on cyclophilin's peptidyl-proline isomerase activity and found that the nucleocapsid (N) protein significantly depends on cyclophilin A (CyPA). We modeled CyPA and N protein interactions to demonstrate the N protein as a potential indirect therapeutic target of CsA, which we propose may impede coronavirus replication by obstructing nucleocapsid folding.RESULTS:
Finally, we analyzed the literature and protein-protein interactions, finding evidence that, by inhibiting CyPA, CsA may impact coagulation proteins and hemostasis.CONCLUSIONS:
Despite CsA's promising antiviral characteristics, the interactions between cyclophilins and coagulation factors emphasize risk stratification for COVID patients with thrombosis dispositions.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Experimental Studies
/
Prognostic study
Language:
English
Journal:
Open Forum Infect Dis
Year:
2021
Document Type:
Article
Affiliation country:
Ofid
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