Journal Article

Antiviral activity of gliotoxin, gentian violet and brilliant green against Nipah and Hendra virus in vitro

Saubern, Simon, Meyer, Adam G, Rootes, Christina L, Porotto, Matteo, Aljofan, Mohamad, Lo, Michael K, Mungall, Bruce A, Sganga, Michael L, Moscona, Anne

2009

Overview

Background Using a recently described monolayer assay amenable to high throughput screening format for the identification of potential Nipah virus and Hendra virus antivirals, we have partially screened a low molecular weight compound library (>8,000 compounds) directly against live virus infection and identified twenty eight promising lead molecules. Initial single blind screens were conducted with 10 μM compound in triplicate with a minimum efficacy of 90% required for lead selection. Lead compounds were then further characterised to determine the median efficacy (IC 50 ), cytotoxicity (CC 50 ) and the in vitro therapeutic index in live virus and pseudotype assay formats. Results While a number of leads were identified, the current work describes three commercially available compounds: brilliant green, gentian violet and gliotoxin, identified as having potent antiviral activity against Nipah and Hendra virus. Similar efficacy was observed against pseudotyped Nipah and Hendra virus, vesicular stomatitis virus and human parainfluenza virus type 3 while only gliotoxin inhibited an influenza A virus suggesting a non-specific, broad spectrum activity for this compound. Conclusion All three of these compounds have been used previously for various aspects of anti-bacterial and anti-fungal therapy and the current results suggest that while unsuitable for internal administration, they may be amenable to topical antiviral applications, or as disinfectants and provide excellent positive controls for future studies.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Animals / Antibacterial agents / Antiviral Agents - chemistry / Antiviral Agents - pharmacology / Biomedical and Life Sciences / Biomedicine / Chlorocebus aethiops / Drug Evaluation, Preclinical / Drug therapy / Genome, Viral - drug effects / Gentian violet / Gentian Violet - chemistry / Gentian Violet - pharmacology / Gliotoxin - chemistry / Gliotoxin - pharmacology / Health aspects / Hendra Virus - drug effects / Henipaviruses / Molecular Structure / Nipah Virus - drug effects / Nipah Virus - genetics / Quaternary Ammonium Compounds - chemistry / Quaternary Ammonium Compounds - pharmacology / Risk factors / RNA virus infections / Vero Cells / Virology