Ribavirin shows antiviral activity against SARS-CoV-2 and downregulates the activity of TMPRSS2 and the expression of ACE2 in vitro
| Autor: | Alpay Azap, Sibel A. Ozkan, Gokce Yagmur Summak, Dunya Aydos, Hasan Nazir, Nil Demir, Merve Murat, Inci Cevher Zeytin, Emek Demir, Julia Somers, Ezgi Goksoy, Açelya Yilmazer, Ceylan Verda Bitirim, Kamil Can Akcali, Zeynep Busra Aksoy Ozer, Aykut Ozkul, Sidar Bereketoglu, Zeynep Eran, Omur Besbinar, Cansu Gurcan, Ebru Kocakaya, Mehmet Ünal |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Physiology medicine.drug_class viruses Guanosine Down-Regulation Pharmacology Antiviral Agents 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Physiology (medical) Chlorocebus aethiops Ribavirin medicine Animals Humans Promoter Regions Genetic Vero Cells chemistry.chemical_classification Messenger RNA SARS-CoV-2 Serine Endopeptidases virus diseases RNA General Medicine biochemical phenomena metabolism and nutrition In vitro G-Quadruplexes 030104 developmental biology Enzyme chemistry 030220 oncology & carcinogenesis Vero cell Angiotensin-Converting Enzyme 2 Antiviral drug Caco-2 Cells |
| Zdroj: | Canadian journal of physiology and pharmacology. 99(5) |
| ISSN: | 1205-7541 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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