Inhibition of hepatitis C virus using siRNA targeted to the virus and Hsp90

Abstract

Hepatitis C (HCV) is a viral disease affecting millions of people worldwide, and persistent HCV infection can lead to progressive liver disease with the development of liver cirrhosis and hepatocellular carcinoma. During treatment for hepatitis C, the occurrence of viral resistance is common. To reduce the occurrence of resistance, new viral treatments should target both viral and cellular factors. Many interactions occur between viral and host proteins during the HCV replication cycle and might be used for the development of new therapies against hepatitis C. Heat shock protein 90 (Hsp90) plays a role in the folding of cellular and viral proteins and also interacts with HCV proteins. In the present study, we knocked down the expression of the Hsp90 gene and inhibited viral replication using siRNA molecules. Reducing the expression of Hsp90 successfully decreased HCV replication. All siRNA molecules specific to the viral genome showed the efficient inhibition of viral replication, particularly siRNA targeted to the 5'UTR region. The combination of siRNAs targeting the viral genome and Hsp90 mRNA also successfully reduced HCV replication and reduced the occurrence of viral resistance. Moreover, these results suggest that an approach based on the combination of cellular and viral siRNAs can be used as an effective alternative for hepatitis C viral suppression.

Expression of Duplex shRNAs through a Lentiviral Vector against Cellular and Viral Genes Inflicts Sustained Inhibition of Hepatitis C Virus Replication

“…2). Simultaneous delivery of multiple siRNA against cellular and/or HCV genomes have shown synergistic inhibition of viral replication [13,44]. Similar reductions of HIV-1 and other viruses have been noted after simultaneous treatment with multiple siRNAs [45,46].…”

An aptamer/ siRNA Chimera against The SARS-CoV-2: A Dual Therapeutic Strategy for The Virus Neutralizing and RNA Interfering

“…RNA interference using siRNAs targeting the viral genome or its key coded proteins has previously been used against some viruses, including SARS-CoV (23)(24)(25)(26)(27). Since SARS-CoV-2 is an RNA virus, either its genome or its key protein expression could be targeted via siRNAs (28).…”

Multiple gene targeting siRNAs for down regulation of Immediate Early-2 (Ie2) and DNA polymerase genes mediated inhibition of novel rat Cytomegalovirus (strain All-03)

“…Viruses evolve to escape from host RNAi by encoding "suppressors of RNAi silencing" (SRS) which is another disadvantage of single usage of siRNA. SiRNA cocktail targeting different region of viral genome lowers the chances of viral mutant formation and prevent viral escape (24)(25)(26)(27). Nevertheless, besides virus infections, siRNAs can be utilized to silence multiple genes at a time which could benefit to treat brain tumorigenesis involving multiple genetic alterations and also targeting a suitable apoptotic gene as a treatment (28,29).…”