Abstract

RNA interference (RNAi) provides the means for alternative antiviral therapy. Delivery of RNAi in the form of short interfering RNA (siRNA), short hairpin RNA (shRNA) and micro-RNA (miRNA) have demonstrated efficacy in gene silencing for therapeutic applications against viral diseases. Bioinformatics has played an important role in the design of efficient RNAi sequences targeting various pathogenic viruses. However, stability and delivery of RNAi molecules have presented serious obstacles for reaching therapeutic efficacy. For this reason, RNA modifications and formulation of nanoparticles have proven useful for non-viral delivery of RNAi molecules. On the other hand, utilization of viral vectors and particularly self-replicating RNA virus vectors can be considered as an attractive alternative. In this review, examples of antiviral therapy applying RNAi-based approaches in various animal models will be described. Due to the current coronavirus pandemic, a special emphasis will be dedicated to targeting Coronavirus Disease-19 (COVID-19).

Highlights

  • Since idoxuridine, the first anti-herpesvirus antiviral drug, reached the market in 1963 more than one hundred antiviral drugs have been formally approved [1]

  • The emphasis in this review has been on antiviral therapeutic applications of RNA interference (RNAi), especially highlighting the application of viral vectors for the delivery of short interfering RNA (siRNA), short hairpin RNA (shRNA) and miRNAs

  • These modifications have improved the delivery of non-viral vectors, the features of superior delivery through highly efficient cell infection and the unmatched expression levels have made the application of viral vectors attractive for RNAi therapy

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Summary

Introduction

The first anti-herpesvirus antiviral drug, reached the market in 1963 more than one hundred antiviral drugs have been formally approved [1]. There is a serious need for development of novel, more efficient antiviral therapies, including drugs and vaccines, which has become even more evident all around the world today due to the recent coronavirus pandemic [2]. In this context, many drugs have been subjected to repurposing such as remdesivir, originally developed for Ebola virus disease (EVD) [3], hydroxychloroquine used for treatment of malaria [4]. Due to the current COVID-19 pandemic, a special emphasis is given to the application of gene silencing for prevention of coronavirus replication as a means for antiviral therapy

RNAi and Gene Silencing
RNAi and Bioinformatics
Delivery of RNAi
Virus-Based RNAi Antiviral Therapy
RNAi-Based Antiviral Therapy Using Non-Viral Delivery
Findings
Conclusions
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