Ribavirin shows antiviral activity against sars-cov-2 and downregulates the activity of tmprss2 and the expression of ace2 in vitro

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

Research output: Contribution to journalArticlepeer-review

Abstract

Ribavirin is a guanosine analog with 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 ribavirin 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 at both mRNA and protein levels 48 h 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 the 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 effects of TMPRSS2 and ACE2 expression.

Original languageEnglish (US)
Pages (from-to)449-460
Number of pages12
JournalCanadian Journal of Physiology and Pharmacology
Volume99
Issue number5
DOIs
StatePublished - 2021

Keywords

  • COVID-19
  • Drug
  • In silico
  • In vitro
  • Pathway analysis

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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