Isocotoin suppresses hepatitis E virus replication through inhibition of heat shock protein 90.

TitleIsocotoin suppresses hepatitis E virus replication through inhibition of heat shock protein 90.
Publication TypeJournal Article
Year of Publication2021
AuthorsNimgaonkar, I, Archer, NF, Becher, I, Shahrad, M, LeDesma, RA, Mateus, A, Caballero-Gómez, J, Berneshawi, AR, Ding, Q, Douam, F, Gaska, JM, Savitski, MM, Kim, H, Ploss, A
JournalAntiviral Res
Volume185
Pagination104997
Date Published2021 01
ISSN1872-9096
KeywordsAntiviral Agents, Cell Line, Tumor, Drug Discovery, Drug Evaluation, Preclinical, Hepatitis E, Hepatitis E virus, High-Throughput Screening Assays, Host Microbial Interactions, HSP90 Heat-Shock Proteins, Humans, Protein Binding, Virus Replication
Abstract

<p>Hepatitis E virus (HEV) causes 14 million infections and 60,000 deaths per year globally, with immunocompromised persons and pregnant women experiencing severe symptoms. Although ribavirin can be used to treat chronic hepatitis E, toxicity in pregnant patients and the emergence of resistant strains are major concerns. Therefore there is an imminent need for effective HEV antiviral agents. The aims of this study were to develop a drug screening platform and to discover novel approaches to targeting steps within the viral life cycle. We developed a screening platform for molecules inhibiting HEV replication and selected a candidate, isocotoin. Isocotoin inhibits HEV replication through interference with heat shock protein 90 (HSP90), a host factor not previously known to be involved in HEV replication. Additional work is required to understand the compound's translational potential, however this suggests that HSP90-modulating molecules, which are in clinical development as anti-cancer agents, may be promising therapies against HEV.</p>

DOI10.1016/j.antiviral.2020.104997
Alternate JournalAntiviral Res
PubMed ID33326835
Grant ListT32 GM007388 / GM / NIGMS NIH HHS / United States