Progress in the experimental therapy of severe arenaviral infections.
ABSTRACT A number of viruses in the family Arenaviridae cause severe illness in humans. Lassa virus in West Africa and a number of agents in South America produce hemorrhagic fever in persons exposed to aerosolized excretions of the pathogens' rodent hosts. Because arenaviruses are not transmitted by arthropods, and person-to-person spread is rare, human infections occur singly and sporadically, and are usually not diagnosed until the patient is severely ill. Because the arenaviruses are naturally transmitted by the airborne route, they also pose a potential threat as aerosolized bioterror weapons. The broad-spectrum antiviral drug ribavirin was shown to reduce mortality from Lassa fever, and has been tested against Argentine hemorrhagic fever, but it is not an approved treatment for either disease. Human immune convalescent plasma was proven to be effective for Argentine hemorrhagic fever in a controlled trial. New treatments are needed to block viral replication without causing toxicity and to prevent the increased vascular permeability that is responsible for hypotension and shock. In this paper, we review current developments in the experimental therapy of severe arenaviral infections, focusing on drugs that have been tested in animal models, and provide a perspective on future research.
SourceAvailable from: Claudia S Sepúlveda[Show abstract] [Hide abstract]
ABSTRACT: Herein, we describe the synthesis of pyrrolo[2,1-b]thiazoles substituted on C-2 or C-5 with a protected carbohydrate moiety. The new fused bicyclic heterocycles were obtained via thiazole intermediates, and the N-alkylation step was assisted by microwave irradiation. The new products were completely characterized by physical and spectroscopic techniques. The cytotoxicity and antiviral activity against Junín virus of the methylated derivates was also evaluated.Journal of Heterocyclic Chemistry 01/2014; DOI:10.1002/jhet.1957 · 0.87 Impact Factor
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ABSTRACT: There are currently no FDA approved vaccines or therapeutics to prevent or treat Argentine Hemorrhagic Fever (AHF). The causative agent of AHF is Junin virus (JUNV); a new world arenavirus classified as an NIAID/CDC Category A priority pathogen. The PTAP Late (L) domain motif within JUNV Z protein facilitates virion egress and transmission by recruiting host Tsg101 and other ESCRT complex proteins to promote scission of the virus particle from the plasma membrane. Here we describe a novel compound (compound 0013) that blocks the JUNV Z-Tsg101 interaction and inhibits budding of virus-like particles (VLPs) driven by ectopic expression of the Z protein and live attenuated JUNV Candid-1 strain in cell culture. As inhibition of the PTAP-Tsg101 interaction inhibits JUNV egress, compound 0013 serves as a prototype therapeutic that could reduce virus dissemination and disease progression in infected individuals. Moreover, since PTAP L-domain-mediated Tsg101 recruitment is utilized by other RNA virus pathogens (e.g. Ebola virus and HIV-1), PTAP inhibitors such as compound 0013 have the potential to function as potent broad-spectrum, host-oriented antiviral drugs. There are currently no FDA approved vaccines or therapeutics to prevent or treat Argentine Hemorrhagic Fever (AHF). The causative agent of AHF is Junin virus (JUNV); a new world arenavirus classified as an NIAID/CDC Category A priority pathogen. Here we describe a prototype therapeutic that blocks budding of JUNV and has the potential to function as a broad-spectrum antiviral drug.Journal of Virology 02/2014; DOI:10.1128/JVI.03757-13 · 4.65 Impact Factor
Chapter: Argentine Hemorrhagic FeverViral Hemorrhagic Fevers, Edited by S.K. Singh & D. Ruzek, 07/2013: chapter 18: pages 317-337; Taylor & Francis Group / CRC Press., ISBN: 13: 978-143-988-429-4