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

Autor: de Vries RD; Department of Viroscience, Erasmus MC, Rotterdam, Netherlands., Schmitz KS; Department of Viroscience, Erasmus MC, Rotterdam, Netherlands., Bovier FT; Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.; Center for Host-Pathogen Interaction, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.; Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli,' Caserta, Italy., Predella C; Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.; Department of Biomedical Engineering, Politecnico di Milano, Milan, Italy., Khao J; Digizyme Inc., Brookline, MA, USA., Noack D; Department of Viroscience, Erasmus MC, Rotterdam, Netherlands., Haagmans BL; Department of Viroscience, Erasmus MC, Rotterdam, Netherlands., Herfst S; Department of Viroscience, Erasmus MC, Rotterdam, Netherlands., Stearns KN; Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.; Center for Host-Pathogen Interaction, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.; Department of Physiology and Cellular Biophysics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA., Drew-Bear J; Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.; Center for Host-Pathogen Interaction, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA., Biswas S; Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, USA., Rockx B; Department of Viroscience, Erasmus MC, Rotterdam, Netherlands., McGill G; Digizyme Inc., Brookline, MA, USA.; Center for Molecular and Cellular Dynamics, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA., Dorrello NV; Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA., Gellman SH; Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA., Alabi CA; Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, USA. caa238@cornell.edu r.deswart@erasmusmc.nl am939@cumc.columbia.edu mp3509@cumc.columbia.edu., de Swart RL; Department of Viroscience, Erasmus MC, Rotterdam, Netherlands. caa238@cornell.edu r.deswart@erasmusmc.nl am939@cumc.columbia.edu mp3509@cumc.columbia.edu., Moscona A; Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. caa238@cornell.edu r.deswart@erasmusmc.nl am939@cumc.columbia.edu mp3509@cumc.columbia.edu.; Center for Host-Pathogen Interaction, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.; Department of Physiology and Cellular Biophysics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.; Department of Microbiology and Immunology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA., Porotto M; Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. caa238@cornell.edu r.deswart@erasmusmc.nl am939@cumc.columbia.edu mp3509@cumc.columbia.edu.; Center for Host-Pathogen Interaction, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.; Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli,' Caserta, Italy.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2021 Mar 26; Vol. 371 (6536), pp. 1379-1382. Date of Electronic Publication: 2021 Feb 17.
DOI: 10.1126/science.abf4896
Abstrakt: Containment of the COVID-19 pandemic requires reducing viral transmission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by membrane fusion between the viral and host cell membranes, which is mediated by the viral spike protein. We have designed lipopeptide fusion inhibitors that block this critical first step of infection and, on the basis of in vitro efficacy and in vivo biodistribution, selected a dimeric form for evaluation in an animal model. Daily intranasal administration to ferrets completely prevented SARS-CoV-2 direct-contact transmission during 24-hour cohousing with infected animals, under stringent conditions that resulted in infection of 100% of untreated animals. These lipopeptides are highly stable and thus may readily translate into safe and effective intranasal prophylaxis to reduce transmission of SARS-CoV-2.
(Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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