Lipidation increases antiviral activities of coronavirus fusion-inhibiting peptides Journal Article

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Authors: Park, J. E.; Gallagher, T.
Article Title: Lipidation increases antiviral activities of coronavirus fusion-inhibiting peptides
Abstract: Coronaviruses (CoVs) can cause life-threatening respiratory diseases. Their infectious entry requires viral spike (S) proteins, which attach to cell receptors, undergo proteolytic cleavage, and then refold in a process that catalyzes virus-cell membrane fusion. Fusion-inhibiting peptides bind to S proteins, interfere with refolding, and prevent infection. Here we conjugated fusion-inhibiting peptides to various lipids, expecting this to secure peptides onto cell membranes and thereby increase antiviral potencies. Cholesterol or palmitate adducts increased antiviral potencies up to 1000-fold. Antiviral effects were evident after S proteolytic cleavage, implying that lipid conjugates affixed the peptides at sites of protease-triggered fusion activation. Unlike lipid-free peptides, the lipopeptides suppressed CoV S protein-directed virus entry taking place within endosomes. Cell imaging revealed intracellular peptide aggregates, consistent with their endocytosis into compartments where CoV entry takes place. These findings suggest that lipidations localize antiviral peptides to protease-rich sites of CoV fusion, thereby protecting cells from diverse CoVs.
Journal Title: Virology
Volume: 511
ISSN: 1096-0341; 0042-6822
Publisher: Elsevier Inc  
Journal Place: United States
Date Published: 2017
Start Page: 9
End Page: 18
Language: eng
DOI/URL:

S0042-6822(17)30252-0
Notes: LR: 20171220; CI: Copyright (c) 2017; GR: P01 AI060699/AI/NIAID NIH HHS/United States; JID: 0110674; 0 (Antiviral Agents); 0 (Lipopeptides); OTO: NOTNLM; 2017/05/17 00:00 [received]; 2017/07/25 00:00 [revised]; 2017/07/27 00:00 [accepted]; 2017/08/13 06:00 [pubmed]; 2017/10/11 06:00 [medline]; 2017/08/13 06:00 [entrez]; ppublish