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

Rory D. de Vries; Katharina S. Schmitz; Francesca T. Bovier; Camilla Predella; Jonathan Khao; Danny Noack; Bart L. Haagmans; Sander Herfst; Kyle N. Stearns; Jennifer Drew-Bear; Sudipta Biswas; Barry Rockx; Gaël McGill; N. Valerio Dorrello; Samuel H. Gellman; Christopher A. Alabi; Rik L. de Swart; Anne Moscona; Matteo Porotto

doi:10.1126/science.abf4896

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

Rory D. de Vries, Katharina S. Schmitz, Francesca T. Bovier, Camilla Predella, Jonathan Khao, Danny Noack, Bart L. Haagmans, Sander Herfst, Kyle N. Stearns, Jennifer Drew-Bear, Sudipta Biswas, Barry Rockx, Gaël McGill, N. Valerio Dorrello, Samuel H. Gellman, Christopher A. Alabi^*, Rik L. de Swart, Anne Moscona, Matteo Porotto

^*Corresponding author for this work

Virology

Research output: Contribution to journal › Article › Academic › peer-review

154 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1379-1382
Number of pages	4
Journal	Science
Volume	371
Issue number	6536
DOIs	https://doi.org/10.1126/science.abf4896
Publication status	Published - 26 Mar 2021

Bibliographical note

Funding Information:
This work was supported by funding from the National Institutes of Health (AI146980, AI121349, and NS091263 to M.P.; AI114736 to A.M.; and HHSN272201400008C to S.H.), the Sharon Golub Fund at Columbia University Irving Medical Center (CUIMC), the Children's Health Innovation Nucleation Fund of the Pediatrics Department at CUIMC, and a Harrington Discovery Institute COVID-19 Award to A.M. A.M. is the inaugural Sherie L. Morrison Professor of Immunology.

Publisher Copyright: © 2021 American Association for the Advancement of Science. All rights reserved.

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de Vries, R. D., Schmitz, K. S., Bovier, F. T., Predella, C., Khao, J., Noack, D., Haagmans, B. L., Herfst, S., Stearns, K. N., Drew-Bear, J., Biswas, S., Rockx, B., McGill, G., Valerio Dorrello, N., Gellman, S. H., Alabi, C. A., de Swart, R. L., Moscona, A., & Porotto, M. (2021). Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets. Science, 371(6536), 1379-1382. https://doi.org/10.1126/science.abf4896

@article{e10654d0e86a406b980159387dbd1999,

title = "Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets",

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.",

author = "{de Vries}, {Rory D.} and Schmitz, {Katharina S.} and Bovier, {Francesca T.} and Camilla Predella and Jonathan Khao and Danny Noack and Haagmans, {Bart L.} and Sander Herfst and Stearns, {Kyle N.} and Jennifer Drew-Bear and Sudipta Biswas and Barry Rockx and Ga{\"e}l McGill and {Valerio Dorrello}, N. and Gellman, {Samuel H.} and Alabi, {Christopher A.} and {de Swart}, {Rik L.} and Anne Moscona and Matteo Porotto",

note = "Funding Information: This work was supported by funding from the National Institutes of Health (AI146980, AI121349, and NS091263 to M.P.; AI114736 to A.M.; and HHSN272201400008C to S.H.), the Sharon Golub Fund at Columbia University Irving Medical Center (CUIMC), the Children's Health Innovation Nucleation Fund of the Pediatrics Department at CUIMC, and a Harrington Discovery Institute COVID-19 Award to A.M. A.M. is the inaugural Sherie L. Morrison Professor of Immunology. Publisher Copyright: {\textcopyright} 2021 American Association for the Advancement of Science. All rights reserved.",

year = "2021",

month = mar,

day = "26",

doi = "10.1126/science.abf4896",

language = "English",

volume = "371",

pages = "1379--1382",

journal = "Science",

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de Vries, RD , Schmitz, KS, Bovier, FT, Predella, C, Khao, J, Noack, D , Haagmans, BL , Herfst, S, Stearns, KN, Drew-Bear, J, Biswas, S, Rockx, B, McGill, G, Valerio Dorrello, N, Gellman, SH, Alabi, CA, de Swart, RL, Moscona, A & Porotto, M 2021, 'Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets', Science, vol. 371, no. 6536, pp. 1379-1382. https://doi.org/10.1126/science.abf4896

TY - JOUR

T1 - Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets

AU - de Vries, Rory D.

AU - Schmitz, Katharina S.

AU - Bovier, Francesca T.

AU - Predella, Camilla

AU - Khao, Jonathan

AU - Noack, Danny

AU - Haagmans, Bart L.

AU - Herfst, Sander

AU - Stearns, Kyle N.

AU - Drew-Bear, Jennifer

AU - Biswas, Sudipta

AU - Rockx, Barry

AU - McGill, Gaël

AU - Valerio Dorrello, N.

AU - Gellman, Samuel H.

AU - Alabi, Christopher A.

AU - de Swart, Rik L.

AU - Moscona, Anne

AU - Porotto, Matteo

N1 - Funding Information: This work was supported by funding from the National Institutes of Health (AI146980, AI121349, and NS091263 to M.P.; AI114736 to A.M.; and HHSN272201400008C to S.H.), the Sharon Golub Fund at Columbia University Irving Medical Center (CUIMC), the Children's Health Innovation Nucleation Fund of the Pediatrics Department at CUIMC, and a Harrington Discovery Institute COVID-19 Award to A.M. A.M. is the inaugural Sherie L. Morrison Professor of Immunology. Publisher Copyright: © 2021 American Association for the Advancement of Science. All rights reserved.

PY - 2021/3/26

Y1 - 2021/3/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85103606306&partnerID=8YFLogxK

U2 - 10.1126/science.abf4896

DO - 10.1126/science.abf4896

M3 - Article

C2 - 33597220

AN - SCOPUS:85103606306

SN - 0036-8075

VL - 371

SP - 1379

EP - 1382

JO - Science

JF - Science

IS - 6536

ER -

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

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