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J Infect Dis ; 221(Supplement_4): S480-S492, 2020 May 11.
Article in English | MEDLINE | ID: mdl-32037447

ABSTRACT

Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that causes fatal encephalitis and respiratory disease in humans. There is currently no approved therapeutic for human use against NiV infection. Griffithsin (GRFT) is high-mannose oligosaccharide binding lectin that has shown in vivo broad-spectrum activity against viruses, including severe acute respiratory syndrome coronavirus, human immunodeficiency virus 1, hepatitis C virus, and Japanese encephalitis virus. In this study, we evaluated the in vitro antiviral activities of GRFT and its synthetic trimeric tandemer (3mG) against NiV and other viruses from 4 virus families. The 3mG had comparatively greater potency than GRFT against NiV due to its enhanced ability to block NiV glycoprotein-induced syncytia formation. Our initial in vivo prophylactic evaluation of an oxidation-resistant GRFT (Q-GRFT) showed significant protection against lethal NiV challenge in Syrian golden hamsters. Our results warrant further development of Q-GRFT and 3mG as potential NiV therapeutics.


Subject(s)
Antiviral Agents/pharmacology , Henipavirus Infections/drug therapy , Nipah Virus/drug effects , Plant Lectins/pharmacology , Virus Internalization/drug effects , Animals , Antiviral Agents/therapeutic use , Chlorocebus aethiops , Disease Models, Animal , Drug Evaluation, Preclinical , Female , HEK293 Cells , HeLa Cells , Henipavirus Infections/virology , Humans , Mesocricetus , Nipah Virus/isolation & purification , Plant Lectins/therapeutic use , Vero Cells
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