SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses.
Animals
Cell Line
Cell Survival
/ drug effects
Hemagglutinin Glycoproteins, Influenza Virus
/ metabolism
Host-Pathogen Interactions
Humans
Influenza A Virus, H1N1 Subtype
/ drug effects
Influenza A Virus, H3N2 Subtype
/ drug effects
Influenza A Virus, H7N9 Subtype
/ drug effects
Influenza A virus
/ drug effects
Membrane Glycoproteins
/ genetics
Metapneumovirus
/ drug effects
Peptide Hydrolases
/ metabolism
Protease Inhibitors
/ pharmacology
Recombinant Proteins
/ pharmacology
Serine Endopeptidases
/ metabolism
Serine Proteinase Inhibitors
/ metabolism
Trypsin Inhibitors
/ metabolism
Viral Fusion Proteins
/ metabolism
Antiviral therapy
HAI-2
HMPV
HMPV F
Hemagglutinin
Influenza
Proteases
SPINT2
Journal
Virology
ISSN: 1096-0341
Titre abrégé: Virology
Pays: United States
ID NLM: 0110674
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
09
10
2019
revised:
25
12
2019
accepted:
04
01
2020
pubmed:
15
2
2020
medline:
2
10
2020
entrez:
15
2
2020
Statut:
ppublish
Résumé
Viruses possessing class I fusion proteins require proteolytic activation by host cell proteases to mediate fusion with the host cell membrane. The mammalian SPINT2 gene encodes a protease inhibitor that targets trypsin-like serine proteases. Here we show the protease inhibitor, SPINT2, restricts cleavage-activation efficiently for a range of influenza viruses and for human metapneumovirus (HMPV). SPINT2 treatment resulted in the cleavage and fusion inhibition of full-length influenza A/CA/04/09 (H1N1) HA, A/Aichi/68 (H3N2) HA, A/Shanghai/2/2013 (H7N9) HA and HMPV F when activated by trypsin, recombinant matriptase or KLK5. We also demonstrate that SPINT2 was able to reduce viral growth of influenza A/CA/04/09 H1N1 and A/X31 H3N2 in cell culture by inhibiting matriptase or TMPRSS2. Moreover, inhibition efficacy did not differ whether SPINT2 was added at the time of infection or 24 h post-infection. Our data suggest that the SPINT2 inhibitor has a strong potential to serve as a novel broad-spectrum antiviral.
Identifiants
pubmed: 32056846
pii: S0042-6822(20)30004-0
doi: 10.1016/j.virol.2020.01.004
pmc: PMC7112099
pii:
doi:
Substances chimiques
Hemagglutinin Glycoproteins, Influenza Virus
0
Membrane Glycoproteins
0
Protease Inhibitors
0
Recombinant Proteins
0
SPINT2 protein, human
0
Serine Proteinase Inhibitors
0
Trypsin Inhibitors
0
Viral Fusion Proteins
0
Peptide Hydrolases
EC 3.4.-
Serine Endopeptidases
EC 3.4.21.-
TMPRSS2 protein, human
EC 3.4.21.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
43-53Subventions
Organisme : NIAID NIH HHS
ID : R21 AI117300
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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