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Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets.
de Vries, Rory D; Schmitz, Katharina S; Bovier, Francesca T; Predella, Camilla; Khao, Jonathan; Noack, Danny; Haagmans, Bart L; Herfst, Sander; Stearns, Kyle N; Drew-Bear, Jennifer; Biswas, Sudipta; Rockx, Barry; McGill, Gaël; Dorrello, N Valerio; Gellman, Samuel H; Alabi, Christopher A; de Swart, Rik L; Moscona, Anne; Porotto, Matteo.
  • 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.
  • Predella C; Center for Host-Pathogen Interaction, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
  • Khao J; Department of Experimental Medicine, University of Campania "Luigi Vanvitelli," Caserta, Italy.
  • Noack D; Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
  • Haagmans BL; Department of Biomedical Engineering, Politecnico di Milano, Milan, Italy.
  • Herfst S; Digizyme Inc., Brookline, MA, USA.
  • Stearns KN; Department of Viroscience, Erasmus MC, Rotterdam, Netherlands.
  • Drew-Bear J; Department of Viroscience, Erasmus MC, Rotterdam, Netherlands.
  • Biswas S; Department of Viroscience, Erasmus MC, Rotterdam, Netherlands.
  • Rockx B; Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
  • McGill G; Center for Host-Pathogen Interaction, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
  • Dorrello NV; Department of Physiology and Cellular Biophysics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
  • Gellman SH; Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
  • Alabi CA; Center for Host-Pathogen Interaction, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
  • de Swart RL; Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, USA.
  • Moscona A; Department of Viroscience, Erasmus MC, Rotterdam, Netherlands.
  • Porotto M; Digizyme Inc., Brookline, MA, USA.
Science ; 371(6536): 1379-1382, 2021 03 26.
Article in English | MEDLINE | ID: covidwho-1476374
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Internalization / Lipopeptides / Viral Fusion Protein Inhibitors / SARS-CoV-2 / COVID-19 / Membrane Fusion Type of study: Experimental Studies Limits: Animals Language: English Journal: Science Year: 2021 Document Type: Article Affiliation country: SCIENCE.ABF4896

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Internalization / Lipopeptides / Viral Fusion Protein Inhibitors / SARS-CoV-2 / COVID-19 / Membrane Fusion Type of study: Experimental Studies Limits: Animals Language: English Journal: Science Year: 2021 Document Type: Article Affiliation country: SCIENCE.ABF4896