Abstract
Among the members of the Arenaviridae family, Lassa virus and Junin virus generate periodic annual outbreaks of severe human hemorrhagic fever (HF) in endemic areas of West Africa and Argentina, respectively. Given the human health threat that arenaviruses represent and the lack of a specific and safe chemotherapy, the search for effective antiviral compounds is a continuous demanding effort. Since diverse host cell pathways and enzymes are used by RNA viruses to fulfill their replicative cycle, the targeting of a host process has turned an attractive antiviral approach in the last years for many unrelated virus types. This strategy has the additional benefit to reduce the serious challenge for therapy of RNA viruses to escape from drug effects through selection of resistant variants triggered by their high mutation rate. This article focuses on novel strategies to identify inhibitors for arenavirus therapy, analyzing the potential for antiviral developments of diverse host factors essential for virus infection.
Highlights
Arenaviruses have turned in recent years a serious and increasing challenge for human public health, in the Americas and Africa
Overexpression of Heterogeneous nuclear ribonucleoproteins (hnRNPs) A1 allowed determining that cells persistently infected with Junin virus (JUNV) do not induce hnRNP A1 cytoplasmic re-localization. These results indicate that hnRNP A1 would favor JUNV productive infection through the interaction with the nucleoprotein
The modulation of survival signaling pathways is a critical event in the replication cycle of arenavirus. Given that these pathways are highly involved in the cell deregulation that occurs during cancer, much progress has been obtained in the development of potential chemotherapy agents against different components of these pathways that might be used as anti-arenaviral drugs
Summary
Arenaviruses have turned in recent years a serious and increasing challenge for human public health, in the Americas and Africa. Besides the critical situation in endemic areas, the high frequency of international air travels has contributed to the importation of arenavirus HF cases into several urban areas around the world [3] In addition to these two pathogens that represent the main health threat in the family, there are four recognized arenaviruses, Sabiá, Guanarito, Machupo and Chapare virus, able to produce very sporadic cases of HF in Brazil, Venezuela and Bolivia, respectively. Antiviral therapies are limited to the use of immune convalescent plasma with defined doses of JUNV-neutralizing antibodies, recommended for Argentine HF patients [2], or the guanosine analog ribavirin (1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) (RIB), effective against Lassa fever by intravenous administration [7]. This article is focused on diverse cellular targets essential for virus infection and their perspectives for specific chemotherapy against arenaviruses
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