Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets

Author:

de Vries Rory D.1ORCID,Schmitz Katharina S.1ORCID,Bovier Francesca T.234ORCID,Predella Camilla25ORCID,Khao Jonathan6ORCID,Noack Danny1ORCID,Haagmans Bart L.1ORCID,Herfst Sander1ORCID,Stearns Kyle N.237ORCID,Drew-Bear Jennifer23,Biswas Sudipta8ORCID,Rockx Barry1ORCID,McGill Gaël69ORCID,Dorrello N. Valerio2ORCID,Gellman Samuel H.10ORCID,Alabi Christopher A.8ORCID,de Swart Rik L.1ORCID,Moscona Anne23711ORCID,Porotto Matteo234ORCID

Affiliation:

1. Department of Viroscience, Erasmus MC, Rotterdam, Netherlands.

2. Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.

3. Center for Host–Pathogen Interaction, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.

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

5. Department of Biomedical Engineering, Politecnico di Milano, Milan, Italy.

6. Digizyme Inc., Brookline, MA, USA.

7. Department of Physiology and Cellular Biophysics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.

8. Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, USA.

9. Center for Molecular and Cellular Dynamics, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.

10. Department of Chemistry, University of Wisconsin–Madison, Madison, WI, USA.

11. Department of Microbiology and Immunology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.

Abstract

Halting transmission The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein binds to host cells and initiates membrane fusion and cell infection. This stage in the virus life history is currently a target for drug inhibition. De Vries et al. designed highly stable lipoprotein fusion inhibitors complementary to a conserved repeat in the C terminus of S that integrate into host cell membranes and inhibit conformational changes in S necessary for membrane fusion. The authors tested the performance of the lipoproteins as a preexposure prophylactic in a ferret-to-ferret transmission study. Intranasal administration of the peptide 2 days before cohousing with an infected ferret for 24 hours completely protected animals in contact from infection and showed efficacy against mutant viruses. Because ferrets do not get sick from SARS-CoV-2, disease prevention could not be tested in this model. Science , this issue p. 1379

Funder

National Institutes of Health

Irving Medical Center, Columbia University

Academia Militar

Harrington Discovery Institute

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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