Antiviral activity of A771726, the active metabolite of leflunomide, against Junín virus

Antiviral activity of A771726, the active metabolite of leflunomide, against Junín virus INTRODUCTIONArenaviruses are enveloped viruses containing a bisegmented single‐stranded RNA genome with an ambisense coding strategy that express four primary viral proteins: the RNA‐dependent RNA polymerase L, the matrix protein Z, the nucleoprotein NP, and the glycoprotein precursor GPC, post‐translationally cleaved to yield the mature virion glycoproteins. Several arenaviruses cause hemorrhagic fevers (HF) with significant level of morbidity and mortality. Among pathogenic arenaviruses, Lassa virus (LASV) and Junín virus (JUNV) are at present the main threat for public health since they generate annual outbreaks of Lassa fever and AHF in endemic areas of West Africa and Argentina, respectively.No specific and safe chemotherapy for any arenavirus is currently available. Treatment is limited to the use of immune convalescent plasma with defined doses of JUNV neutralizing antibodies for AHF or the guanosine analog ribavirin, effective against several RNA viruses including LASV. However, several drawbacks are associated to both treatments, such as failure in advanced infections and undesirable side effects. Then, there is a real need of novel therapeutic options against arenaviruses.In the search of effective and safe antiviral agents, the consideration of host factors involved in virus replication that are known or predicted to bind to a drug as therapeutic targets has http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Medical Virology Wiley

Antiviral activity of A771726, the active metabolite of leflunomide, against Junín virus

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Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
© 2018 Wiley Periodicals, Inc.
ISSN
0146-6615
eISSN
1096-9071
D.O.I.
10.1002/jmv.25024
Publisher site
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Abstract

INTRODUCTIONArenaviruses are enveloped viruses containing a bisegmented single‐stranded RNA genome with an ambisense coding strategy that express four primary viral proteins: the RNA‐dependent RNA polymerase L, the matrix protein Z, the nucleoprotein NP, and the glycoprotein precursor GPC, post‐translationally cleaved to yield the mature virion glycoproteins. Several arenaviruses cause hemorrhagic fevers (HF) with significant level of morbidity and mortality. Among pathogenic arenaviruses, Lassa virus (LASV) and Junín virus (JUNV) are at present the main threat for public health since they generate annual outbreaks of Lassa fever and AHF in endemic areas of West Africa and Argentina, respectively.No specific and safe chemotherapy for any arenavirus is currently available. Treatment is limited to the use of immune convalescent plasma with defined doses of JUNV neutralizing antibodies for AHF or the guanosine analog ribavirin, effective against several RNA viruses including LASV. However, several drawbacks are associated to both treatments, such as failure in advanced infections and undesirable side effects. Then, there is a real need of novel therapeutic options against arenaviruses.In the search of effective and safe antiviral agents, the consideration of host factors involved in virus replication that are known or predicted to bind to a drug as therapeutic targets has

Journal

Journal of Medical VirologyWiley

Published: Jan 1, 2018

Keywords: ; ; ; ; ;

References

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