Abstract
Ecological changes, population movements and increasing urbanization promote the expansion of hantaviruses, placing humans at high risk of virus transmission and consequent diseases. The currently limited therapeutic options make the development of antiviral strategies an urgent need. Ribavirin is the only antiviral used currently to treat hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus (HTNV), even though severe side effects are associated with this drug. We therefore investigated the antiviral activity of favipiravir, a new antiviral agent against RNA viruses. Both ribavirin and favipiravir demonstrated similar potent antiviral activity on HTNV infection. When combined, the efficacy of ribavirin is enhanced through the addition of low dose favipiravir, highlighting the possibility to provide better treatment than is currently available.
Highlights
Orthohantaviruses are emerging negativestrand RNA viruses associated with two life-threatening diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS)
As ribavirin is the standard treatment for HFRS disease, and that T-705 is a potent novel antiviral against Hantaan virus (HTNV) infection, we investigated whether T-705 would result in a synergistic, additive, or antagonistic effect with ribavirin
Hantaan virus (HTNV) is responsible of HFRS, a severe human disease and the therapeutic approaches currently used are limited to supportive care, highlighting the need for novel therapeutic strategies against pathogenic HTNV
Summary
Orthohantaviruses (hereafter referred to as hantaviruses) are emerging negativestrand RNA viruses associated with two life-threatening diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). Old World hantaviruses, including the prototypic Hantaan virus (HTNV) and Seoul virus (SEOV) are widespread in Asia where they can cause HFRS with up to 15% case-fatality. The New. World hantaviruses Sin Nombre (SNV) and Andes (ANDV) are associated with HCPS in the Americas with up to 40% mortality. Rodents and insectivores represent the natural reservoir of hantaviruses, in which infections are persistent but asymptomatic. Humans’ infection is mainly transmitted by direct inhalation of contaminated rodent excreta [2,3], while human-to-human transmission has been reported for ANDV via close contact with symptomatic persons [4,5,6,7]
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