The Antiviral Properties of Cyclosporine. Focus on Coronavirus, Hepatitis C Virus, Influenza Virus, and Human Immunodeficiency Virus Infections

Abstract

This review updates current knowledge regarding the risk of viral infections, including COVID-19, in patients treated with cyclosporine. We also shortly refer to bacterial infections and parasitic infestations in patients treated with cyclosporin. Cyclosporine is an immunosuppressive drug, which is widely used in medicine, including in the treatment of autoimmune skin diseases in dermatology, rheumatology, ophthalmology and nephrology, and in organ transplantation. A usual concern associated with immunosuppressive treatment is the potential risk of infections. Interestingly, several data indicate a relatively low risk of infections, especially viral infections, in patients receiving cyclosporine. It was shown that cyclosporine exerts an inhibitory effect on the replication of some viruses, or may have a potentially beneficial effect on the disease course in infections. These include hepatitis C, influenza virus, rotavirus, human immunodeficiency virus and coronavirus infections. Available data indicate that cyclosporine may have a beneficial effect on COVID-19, which is caused by the coronavirus SARS-COV2.

Impact of SARS-CoV-2 Pandemic on Patients with Primary Immunodeficiency

“…The current knowledge about COVID-19 in cases with underlying immunodeficiency is scarce [18][19][20][21][22][23][24]. Comparing to previous data reported mainly primary antibody deficient and male patients with COVID-19 infection (Table S4), we did not observe the dominancy of infected patients in this PID category despite their high frequency among the national registry with no deceased patient.…”

Mitochondrial Ion Channels of the Inner Membrane and Their Regulation in Cell Death Signaling

“…Virus infections promote BAX translocation and, in turn, MOMP and PTP activation, eventually leading to cytochrome c release ( Lee and Lee, 2018 ); CsA treatment efficiently inhibited both virus replication/infection and host cell death. Despite this, it is still unclear if CsA treatment prevents apoptosis by sequestering CyPD (with direct implication in PTP opening) or CyPA (affecting virus replication and BAX translocation) ( Glowacka et al, 2020 ; Molyvdas and Matalon, 2020 ).…”

Drawing Comparisons between SARS-CoV-2 and the Animal Coronaviruses

“…Cyclophilin inhibitors (Cyclosporine A and analogues such as Alisporivir) are immunosuppressive drugs with anti-calcineurin properties [ 194 ]. Alisporivir has been shown to exhibit strong, dose-dependent antiviral activity against SARS-CoV-2 in vitro, and is being considered for a phase-2, proof-of-concept clinical trial [ 195 , 196 ].…”

“…Alisporivir has been shown to exhibit strong, dose-dependent antiviral activity against SARS-CoV-2 in vitro, and is being considered for a phase-2, proof-of-concept clinical trial [ 195 , 196 ]. However, concerns have been raised about the safety of cyclosporine in SARS-CoV-2 patients [ 194 ]. Previously, cyclophilin inhibitors have been shown to inhibit the replication of animal CoVs (FCoV, IBV, and MHV) and human CoVs (HCoV-229E, HCoV-NL63, MERS-CoV, and SARS-CoV) [ 194 , 195 , 197 ].…”