Enhancing the solubility of SARS-CoV-2 inhibitors to increase future prospects for clinical development

Despite the existence of vaccines for SARS-CoV-2, the constant evolution of new variants and the occurrence of breakthrough infections highlight the need for new and effective antiviral approaches. We have shown that lipopeptides designed to bind a conserved region on the SARS-CoV-2 spike protein ca...

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Vydáno v:Journal of virology Ročník 99; číslo 3; s. e0215924
Hlavní autoři: Kuhn, Ariel J., Outlaw, Victor K., Marcink, Tara C., Yu, Zhen, Mears, Megan C., Cajimat, Maria N., Kreitler, Dale F., Cleven, Payton R., Mook, Jee Ching, Bente, Dennis A., Porotto, Matteo, Gellman, Samuel H., Moscona, Anne
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States American Society for Microbiology 18.03.2025
Témata:
antiviral
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
COVID-19 - virology
COVID-19 Drug Treatment
crystal structure
Editor’s Pick
heptad repeats
Humans
inhibitors
lipopeptide
Lipopeptides - chemistry
Lipopeptides - pharmacology
MATERIALS SCIENCE
peptide design
SARS-CoV-2
SARS-CoV-2 - drug effects
Solubility
Spike Glycoprotein, Coronavirus - antagonists & inhibitors
Spike Glycoprotein, Coronavirus - chemistry
Spike Glycoprotein, Coronavirus - metabolism
Vaccines and Antiviral Agents
viral fusion
Virology
Virus Internalization - drug effects
inhibitors
SARS-CoV-2
lipopeptide
antiviral
viral fusion
crystal structure
peptide design
solubility
heptad repeats
ISSN:0022-538X, 1098-5514, 1098-5514
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Popis
Shrnutí:Despite the existence of vaccines for SARS-CoV-2, the constant evolution of new variants and the occurrence of breakthrough infections highlight the need for new and effective antiviral approaches. We have shown that lipopeptides designed to bind a conserved region on the SARS-CoV-2 spike protein can effectively block viral entry into cells and thereby block infection. To support the feasibility of using this approach in humans, we re-designed these lipopeptides to be more soluble, using information about the structure of the spike protein interacting with the peptides to modify the peptide chain. The new peptides are effective against both SARS-CoV-2 and MERS. The lipopeptides described here could serve as treatment for people who are unvaccinated or who experience breakthrough infections, and the approach to increasing solubility can be applied in a broad spectrum approach to treating infections with emerging viruses.
Bibliografie:ObjectType-Article-1
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USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)
BNL--227607-2025-JAAM
SC0012704
National Institutes of Health (NIH)
USDOE Office of Science (SC), Biological and Environmental Research (BER)
Present address: U.S. Department of Agriculture, Athens, Georgia, USA
Present address: Department of Chemistry, University of Missouri, Columbia, Missouri, USA
Anne Moscona and Matteo Porotto hold stock options in a start up company (Thylacine Biosciences) that aims to develop peptide antivirals but does not utilize the technology described in this work.
Ariel J. Kuhn, Victor K. Outlaw, and Tara C. Marcink contributed equally to this article. Author order was determined by nature of contribution.
ISSN:0022-538X
1098-5514
1098-5514
DOI:10.1128/jvi.02159-24