Abstract
Andes virus (ANDV) and Sin Nombre virus (SNV), highly pathogenic hantaviruses, cause hantavirus pulmonary syndrome in the Americas. Currently no therapeutics are approved for use against these infections. Griffithsin (GRFT) is a high-mannose oligosaccharide-binding lectin currently being evaluated in phase I clinical trials as a topical microbicide for the prevention of human immunodeficiency virus (HIV-1) infection (ClinicalTrials.gov Identifiers: NCT04032717, NCT02875119) and has shown broad-spectrum in vivo activity against other viruses, including severe acute respiratory syndrome coronavirus, hepatitis C virus, Japanese encephalitis virus, and Nipah virus. In this study, we evaluated the in vitro antiviral activity of GRFT and its synthetic trimeric tandemer 3mGRFT against ANDV and SNV. Our results demonstrate that GRFT is a potent inhibitor of ANDV infection. GRFT inhibited entry of pseudo-particles typed with ANDV envelope glycoprotein into host cells, suggesting that it inhibits viral envelope protein function during entry. 3mGRFT is more potent than GRFT against ANDV and SNV infection. Our results warrant the testing of GRFT and 3mGRFT against ANDV infection in animal models.
Highlights
Andes virus (ANDV) and Sin Nombre virus (SNV) are zoonotic orthohantaviruses harbored by rodents and are responsible for nearly annual outbreaks of fatal human pulmonary syndrome disease in the Americas (Schmaljohn and Hjelle, 1997; Hooper et al, 2001; Jonsson et al, 2008; Brocato and Hooper, 2019)
Seventytwo hours later, cells were fixed, permeabilized, and stained with an antibody raised against the nucleoprotein of Puumala virus that cross-reacts with nucleoproteins of other hantaviruses like ANDV and SNV
The observed EC50 values of these compounds against ANDV were well within the range of those reported for other enveloped viruses (Meuleman et al, 2011; Ishag et al, 2016; Millet et al, 2016; Lo et al, 2020). Using both infectious virions and pseudoparticle systems, we clearly demonstrate that GRFT can inhibit ANDV infection at the level of virus entry
Summary
Andes virus (ANDV) and Sin Nombre virus (SNV) are zoonotic orthohantaviruses (referred here as hantaviruses) harbored by rodents and are responsible for nearly annual outbreaks of fatal human pulmonary syndrome disease in the Americas (Schmaljohn and Hjelle, 1997; Hooper et al, 2001; Jonsson et al, 2008; Brocato and Hooper, 2019). Several therapeutics protect against lethal ANDV challenge in animals (Safronetz et al, 2013; Bird et al, 2016) none is currently approved for human use except for ribavirin, which is effective only when given early in the disease course (Chapman et al, 1999; Mertz et al, 2004). It has demonstrated broad-spectrum activity in vitro and in vivo against viruses including severe
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