Ribavirin shows antiviral activity against SARS-CoV-2 and downregulates the activity of TMPRSS2 and the expression of ACE2 In Vitro.

Unal, Mehmet Altay; Bitirim, Ceylan Verda; Summak, Gokce Yagmur; Bereketoglu, Sidar; Cevher Zeytin, Inci; Besbİnar, Omur; Gurcan, Cansu; Aydos, Dunya; Goksoy, Ezgi; Kocakaya, Ebru; Eran, Zeynep; Murat, Merve; Demir, Nil; Aksoy Ozer, Zeynep Busra; Somers, Julia; Demir, Emek; Nazir, Hasan; Ozkan, Sibel Aysil; Ozkul, Aykut; Azap, Alpay; Yilmazer, Açelya; Akcali, Kamil Can

Ribavirin is a guanosine analog and has a broad-spectrum antiviral activity against RNA viruses. Based on this, we aimed to show the anti-SARS-CoV-2 activity of this drug molecule via in vitro, in silico and molecular techniques. Ribavirin showed antiviral activity in Vero E6 cells following SARS-CoV-2 infection whereas the drug itself did not show any toxic effect over the concentration range tested. In silico analysis suggested that Ribarivin has a broad-spectrum impact on SARS-CoV-2, acting at different viral proteins. According to the detailed molecular techniques, Ribavirin was shown to decrease the expression of TMPRSS2 both at mRNA and protein levels 48 hours after treatment. The suppressive effect of Ribavirin in ACE2 protein expression was shown to be dependent on cell types. Finally, proteolytic activity assays showed that Ribavirin also showed an inhibitory effect on TMPRSS2 enzyme. Based on these results, we hypothesized that Ribavirin may inhibit the expression of TMPRSS2 by modulating the formation of inhibitory G-quadruplex structures at the TMPRSS2 promoter. As a conclusion, Ribavirin is a potential antiviral drug for the treatment against SARS-CoV-2, and it interferes with the effect of TMPRSS2 and ACE2 expression.