Year: 2019
Type: article
Abstract: Emerging human-pathogenic arenaviruses are causative agents of severe hemorrhagic fevers with high mortality and represent serious public health problems. The current lack of a licensed vaccine and the limited treatment options makes the development of novel antiarenaviral therapeutics an urgent need. Using a recombinant pseudotype platform, we uncovered that clotrimazole drugs, in particular TRAM-34, specifically inhibit cell entry of a range of arenaviruses, including important emerging human pathogens, with the exception of Lassa virus. The antiviral effect was independent of the known pharmacological drug target and involved inhibition of the unusual membrane fusion mechanism of arenaviruses. TRAM-34 and its derivatives currently undergo evaluation against a number of human diseases and show favorable toxicity profiles and high stability in vivo . Our study provides the basis for further evaluation of clotrimazole derivatives as antiviral drug candidates. Their advanced stage of drug development will facilitate repurposing for therapeutic intervention against human-pathogenic arenaviruses.
Source: Journal of Virology
DOI: 10.1128/jvi.01744-18
Language: English
Topic: Viral Infections and Vectors
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Unraveling the mechanisms of HDL-mediated pancreatic beta cell protection, Host cell invasion by Lassa virus, Host cell invasion by Lassa virus, G5974836772, Paramyxovirus cell exit: from basics to drug discovery strategies, G7382320639, G8390223305, The caspase-3/RasGAP stress sensor module and the control of cell metabolism, G8690818240
OpenAlex ID: W2908884740