Inhibition of Coronavirus Entry In Vitro and Ex Vivo by a Lipid-Conjugated Peptide Derived from the SARS-CoV-2 Spike Glycoprotein HRC Domain

Author:

Outlaw Victor K.1ORCID,Bovier Francesca T.234,Mears Megan C.56,Cajimat Maria N.56,Zhu Yun237,Lin Michelle J.8,Addetia Amin8,Lieberman Nicole A. P.8,Peddu Vikas8,Xie Xuping29ORCID,Shi Pei-Yong29,Greninger Alexander L.810ORCID,Gellman Samuel H.1,Bente Dennis A.511,Moscona Anne231213,Porotto Matteo234

Affiliation:

1. Department of Chemistry, University of Wisconsin, Madison, Wisconsin, USA

2. Department of Pediatrics, Columbia University Medical Center, New York, New York, USA

3. Center for Host-Pathogen Interaction, Columbia University Medical Center, New York, New York, USA

4. Department of Experimental Medicine, University of Campania “Luigi Vanvitelli,” Caserta, Italy

5. Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA

6. Department of Experimental Pathology, University of Texas Medical Branch, Galveston, Texas, USA

7. Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, Beijing, China

8. Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington, USA

9. Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA

10. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

11. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA

12. Department of Microbiology & Immunology, Columbia University Medical Center, New York, New York, USA

13. Department of Physiology & Cellular Biophysics, Columbia University Medical Center, New York, New York, USA

Abstract

SARS-CoV-2, the causative agent of COVID-19, continues to spread globally, placing strain on health care systems and resulting in rapidly increasing numbers of cases and mortalities. Despite the growing need for medical intervention, no FDA-approved vaccines are yet available, and treatment has been limited to supportive therapy for the alleviation of symptoms. Entry inhibitors could fill the important role of preventing initial infection and preventing spread. Here, we describe the design, synthesis, and evaluation of a lipopeptide that is derived from the HRC domain of the SARS-CoV-2 S glycoprotein that potently inhibits fusion mediated by SARS-CoV-2 S glycoprotein and blocks infection by live SARS-CoV-2 in both cell monolayers ( in vitro ) and human airway tissues ( ex vivo ). Our results highlight the SARS-CoV-2 HRC-derived lipopeptide as a promising therapeutic candidate for SARS-CoV-2 infections.

Funder

HHS | National Institutes of Health

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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