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The Cyclophilin-Dependent Calcineurin Inhibitor Voclosporin Inhibits SARS-CoV-2 Replication in Cell Culture.
Ogando, Natacha S; Metscher, Erik; Moes, Dirk Jan A R; Arends, Eline J; Tas, Ali; Cross, Jennifer; Snijder, Eric J; Teng, Y K Onno; de Vries, Aiko P J; van Hemert, Martijn J.
  • Ogando NS; Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands.
  • Metscher E; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands.
  • Moes DJAR; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands.
  • Arends EJ; Leiden Transplant Center, Leiden University Medical Center, Leiden, Netherlands.
  • Tas A; Department of Nephrology, Leiden University Medical Center, Leiden, Netherlands.
  • Cross J; Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands.
  • Snijder EJ; Aurinia Pharmaceuticals Inc., Victoria, BC, Canada.
  • Teng YKO; Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands.
  • de Vries APJ; Leiden Transplant Center, Leiden University Medical Center, Leiden, Netherlands.
  • van Hemert MJ; Department of Nephrology, Leiden University Medical Center, Leiden, Netherlands.
Transpl Int ; 35: 10369, 2022.
Article in English | MEDLINE | ID: covidwho-1933952
ABSTRACT
Kidney transplant recipients (KTRs) are at increased risk for a more severe course of COVID-19, due to their pre-existing comorbidity and immunosuppression. Consensus protocols recommend lowering immunosuppression in KTRs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the optimal combination remains unclear. Calcineurin inhibitors (CNIs) are cornerstone immunosuppressants used in KTRs and some have been reported to possess antiviral activity against RNA viruses, including coronaviruses. Here, we evaluated the effect of the CNIs tacrolimus, cyclosporin A, and voclosporin (VCS), as well as other immunosuppressants, on SARS-CoV-2 replication in cell-based assays. Unexpected, loss of compound due to plastic binding and interference of excipients in pharmaceutical formulations (false-positive results) complicated the determination of EC50 values of cyclophilin-dependent CNI's in our antiviral assays. Some issues could be circumvented by using exclusively glass lab ware with pure compounds. In these experiments, VCS reduced viral progeny yields in human Calu-3 cells at low micromolar concentrations and did so more effectively than cyclosporin A, tacrolimus or other immunosuppressants. Although, we cannot recommend a particular immunosuppressive regimen in KTRs with COVID-19, our data suggest a potential benefit of cyclophilin-dependent CNIs, in particular VCS in reducing viral progeny, which warrants further clinical evaluation in SARS-CoV-2-infected KTRs.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Experimental Studies / Prognostic study Limits: Humans Language: English Journal: Transpl Int Journal subject: Transplantation Year: 2022 Document Type: Article Affiliation country: Ti.2022.10369

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Experimental Studies / Prognostic study Limits: Humans Language: English Journal: Transpl Int Journal subject: Transplantation Year: 2022 Document Type: Article Affiliation country: Ti.2022.10369