PubMed Journals: J Infect Dis
Source: PMID: 32037447
⇦ ⇨ J Infect Dis. 2020 Feb 10. pii: jiz630. doi:
⇩ 10.1093/infdis/jiz630. [Epub ahead of print]
Griffithsin Inhibits Nipah Virus Entry and Fusion
and Can Protect Syrian Golden Hamsters From
Lethal Nipah Virus Challenge.
Lo MK(1), Spengler JR(1), Krumpe LRH(2),
Welch SR(1), Chattopadhyay A(3), Harmon
JR(1), Coleman-McCray JD(1), Scholte FEM(1),
Hotard AL(1), Fuqua JL(4), Rose JK(3), Nichol
ST(1), Palmer KE(4), O'Keefe BR(5)(6),
(1) Viral Special Pathogens Branch, Division of
High-Consequence Pathogens and Pathology,
National Center for Emerging and Zoonotic
Centers for Disease Control and Prevention,
Atlanta, Georgia, USA.
(2) Basic Science Program, Frederick National
Laboratory for Cancer Research, Frederick,
(3) Yale University School of Medicine, New
Haven, Connecticut, USA.
(4) Center for Predictive Medicine for
Biodefense and Emerging Infectious Diseases,
University of Louisville School of Medicine,
Louisville, Kentucky, USA.
(5) Molecular Targets Program, Center for
Cancer Research, National Cancer Institute,
Frederick, Maryland, USA.
(6) Natural Products Branch, Developmental
Therapeutics Program, Division of Cancer
Treatment and Diagnosis, National Cancer
Institute, Frederick, Maryland, USA.
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 across 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.
©The Author(s) 2020. Published by Oxford
University Press for the Infectious Diseases
Society of America. All rights reserved. For
DOI: 10.1093/infdis/jiz630 PMID: 32037447