Translation of Mycobacterium Survival Strategy to Develop a Lipo-peptide based Fusion Inhibitor*.
Animals
Antiviral Agents
/ chemistry
Dipeptides
/ chemistry
Dogs
Humans
Influenza A Virus, H1N1 Subtype
/ drug effects
Lipopeptides
/ chemistry
Liposomes
/ chemistry
Madin Darby Canine Kidney Cells
Membrane Fusion
/ drug effects
Murine hepatitis virus
/ drug effects
Phosphatidylcholines
/ chemistry
Phosphatidylethanolamines
/ chemistry
Rats
Virus Internalization
/ drug effects
broad-spectrum antivirals
enveloped virus
lipo-peptide inhibitor
membrane fusion
water penetration
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
08 03 2021
08 03 2021
Historique:
received:
14
10
2020
pubmed:
27
11
2020
medline:
10
3
2021
entrez:
26
11
2020
Statut:
ppublish
Résumé
The entry of enveloped virus requires the fusion of viral and host cell membranes. An effective fusion inhibitor aiming at impeding such membrane fusion may emerge as a broad-spectrum antiviral agent against a wide range of viral infections. Mycobacterium survives inside the phagosome by inhibiting phagosome-lysosome fusion with the help of a coat protein coronin 1. Structural analysis of coronin 1 and other WD40-repeat protein suggest that the trp-asp (WD) sequence is placed at distorted β-meander motif (more exposed) in coronin 1. The unique structural feature of coronin 1 was explored to identify a simple lipo-peptide sequence (myr-WD), which effectively inhibits membrane fusion by modulating the interfacial order, water penetration, and surface potential. The mycobacterium inspired lipo-dipeptide was successfully tested to combat type 1 influenza virus (H1N1) and murine coronavirus infections as a potential broad-spectrum antiviral agent.
Identifiants
pubmed: 33241871
doi: 10.1002/anie.202013848
pmc: PMC7753697
doi:
Substances chimiques
Antiviral Agents
0
Dipeptides
0
Lipopeptides
0
Liposomes
0
Phosphatidylcholines
0
Phosphatidylethanolamines
0
dioleoyl phosphatidylethanolamine
2462-63-7
1,2-oleoylphosphatidylcholine
EDS2L3ODLV
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6101-6106Subventions
Organisme : DST-INSPIRE
ID : IFA13-CH-120, 2014
Organisme : SERB-ECA
ID : ECR/2016/001935
Informations de copyright
© 2020 Wiley-VCH GmbH.
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