tetano
Editor, Senior Moderator
Open Forum Infect Dis
. 2021 Apr 14;8(6)
fab189.
doi: 10.1093/ofid/ofab189. eCollection 2021 Jun.
In Silico Evaluation of Cyclophilin Inhibitors as Potential Treatment for SARS-CoV-2
Kyle Laurie[SUP] 1 [/SUP], David Holcomb[SUP] 1 [/SUP], Jacob Kames[SUP] 1 [/SUP], Anton A Komar[SUP] 2 [/SUP], Michael DiCuccio[SUP] 3 [/SUP], Juan C Ibla[SUP] 4 [/SUP], Chava Kimchi-Sarfaty[SUP] 1 [/SUP]
Affiliations
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.
Keywords: ADAMTS13; COVID-19; antiviral; coagulopathy; cyclophilin; cyclosporine A.
. 2021 Apr 14;8(6)
fab189.doi: 10.1093/ofid/ofab189. eCollection 2021 Jun.
In Silico Evaluation of Cyclophilin Inhibitors as Potential Treatment for SARS-CoV-2
Kyle Laurie[SUP] 1 [/SUP], David Holcomb[SUP] 1 [/SUP], Jacob Kames[SUP] 1 [/SUP], Anton A Komar[SUP] 2 [/SUP], Michael DiCuccio[SUP] 3 [/SUP], Juan C Ibla[SUP] 4 [/SUP], Chava Kimchi-Sarfaty[SUP] 1 [/SUP]
Affiliations
- PMID: 34109257
- PMCID: PMC8083350
- DOI: 10.1093/ofid/ofab189
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.
Keywords: ADAMTS13; COVID-19; antiviral; coagulopathy; cyclophilin; cyclosporine A.