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Antiviral screening identifies adenosine analogs targeting the endogenous dsRNA Leishmania RNA virus 1 (LRV1) pathogenicity factor

Year: 2017

Type: article

Abstract: Significance The endogenous double-stranded RNA virus Leishmaniavirus (LRV1) has been implicated as a pathogenicity factor for leishmaniasis in rodent models and human disease, and associated with drug-treatment failures. As a first step toward the identification of therapeutic LRV1 inhibitors, we identified two adenosine analogs that selectively inhibited LRV1 replication. These analogs were used as tools to confirm that viral inheritance is by random segregation, as well as to generate LRV1-cured lines of Leishmania guyanensis, which correspondingly lost the increased pathogenicity conferred by LRV1. These compounds hold promise as leads to ameliorate the severity of LRV1-bearing Leishmania infections, and raise the possibility of targeting other protozoal infections whose pathogenicity may be exacerbated by similar endogenous viruses.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1619114114

Authors: F. Matthew Kuhlmann, John I. Robinson, Gregory R. Bluemling, Catherine Ronet, Nicolas Fasel, Stephen M. Beverley

Institutions: Washington University in St. Louis, Emory University, University of Lausanne

Language: English

Topic: Research on Leishmaniasis Studies

Subfield: Public Health, Environmental and Occupational Health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Fonds De La Recherche Scientifique - FNRS, National Institute of Allergy and Infectious Diseases