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; Zeytin, Inci Cevher; Bul, Omur; Gurcan, Cansu; Aydos, Dunya; Goksoy, Ezgi; Kocakaya, Ebru; Eran, Zeynep; Murat, Merve; Demir, Nil; Somers, Julia; Demir, Emek; Nazir, Hasan; Ozkan, Sibel Aysil; Ozkul, Aykut; Azap, Alpay; Yilmazer, Acelya; 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. In silico analysis suggested that Ribarivin has a broad-spectrum impact on Vero E6 cells. According to the detailed molecular techniques, Ribavirin was shown to decrease TMPRSS2 expression both at mRNA and protein level 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. 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.