Host Proteins Identified in Extracellular Viral Particles as Targets for Broad-Spectrum Antiviral Inhibitors.

Abstract

Liquid chromatography mass spectrometry (LCMS) proteomic analyses have revealed that host proteins are often captured in extracellular virions. These proteins may play a role in viral replication or infectivity and can represent targets for broad-spectrum antiviral agent development. We utilized LCMS to determine the host protein composition of Lassa virus-like particles (LASV VLPs). Multiple host proteins incorporated in LASV VLPs are also incorporated in unrelated viruses, notably ribosomal proteins. We assembled a data set of host proteins incorporated into extracellular viral particles. The frequent incorporation of specific host proteins into viruses of diverse families suggests that interactions of these proteins with viral factors may be important for effective viral replication. Drugs that target virion-associated host proteins could affect the protein in the extracellular virion or the host cell. Compounds that target proteins incorporated into virions with high frequency, but with no known antiviral activity, were assayed in a scalable viral screening platform, and hits were tested in competent viral systems. One of these molecules, GAPDH modulating small molecule CGP 3466B maleate (Omigapil), exhibited a dose-dependent inhibition of HIV, dengue virus, and Zika virus.