Development of a mass screening system for antiviral drug discovery using viral hemorrhagic septicemia virus as an RNA virus surrogate

Abstract

Viruses are intracellular pathogens that cannot reproduce on their own outside of their host. Viruses frequently mutate due to their rapid replication rate. These genetically modified viruses often acquire cross-species infectivity, making existing vaccines useless. Therefore, there is a need for a broad range of antiviral drugs that act on various viral infections. In this study, a recombinant viral hemorrhagic septicemia virus (rVHSV) expressing an enhanced green fluorescence protein (eGFP), with no risk to human infection, was used as an RNA surrogate virus. We developed a fluorescence and CPE-based high-throughput screening (HTS) system capable of screening large-scale libraries for the development of a wide range of antiviral drugs for common RNA viruses. Total substance libraries of 15,635 chemical compounds and 3,498 extracts of plants and marine organisms were screened using this system and 27 substances showed antiviral activity against rVHSV. Among them, two chemicals and two extracts were selected as the final candidates based on their antiviral activity at low concentrations. Because the antiviral activity of these substances has not been reported, they could be potential antiviral agents for the treatment of RNA virus infections.