De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2-Reference-Cited by-同舟云学术

De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2

Published:2020-12-04 Issue:6521 Volume:370 Page:1208-1214
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Linsky Thomas W.¹^ORCID,Vergara Renan¹^ORCID,Codina Nuria¹^ORCID,Nelson Jorgen W.¹^ORCID,Walker Matthew J.¹^ORCID,Su Wen²^ORCID,Barnes Christopher O.³,Hsiang Tien-Ying⁴^ORCID,Esser-Nobis Katharina⁴^ORCID,Yu Kevin¹^ORCID,Reneer Z. Beau⁵^ORCID,Hou Yixuan J.⁴^ORCID,Priya Tanu¹,Mitsumoto Masaya¹,Pong Avery¹,Lau Uland Y.¹^ORCID,Mason Marsha L.¹^ORCID,Chen Jerry¹^ORCID,Chen Alex¹,Berrocal Tania¹^ORCID,Peng Hong¹,Clairmont Nicole S.¹,Castellanos Javier¹,Lin Yu-Ru¹,Josephson-Day Anna¹^ORCID,Baric Ralph S.⁶^ORCID,Fuller Deborah H.⁷^ORCID,Walkey Carl D.¹,Ross Ted M.⁵⁸,Swanson Ryan¹^ORCID,Bjorkman Pamela J.³^ORCID,Gale Michael⁴^ORCID,Blancas-Mejia Luis M.¹^ORCID,Yen Hui-Ling²^ORCID,Silva Daniel-Adriano¹^ORCID

Affiliation:

1. Neoleukin Therapeutics Inc., Seattle, WA, USA.

2. School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China.

3. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.

4. Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA, USA.

5. Center for Vaccines and Immunology, University of Georgia, Athens, GA, USA.

6. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

7. Department of Microbiology, University of Washington, Seattle, WA, USA.

8. Department of Infectious Diseases, University of Georgia, Athens, GA, USA.

Abstract

A decoy to neutralize SARS-CoV-2 Many efforts to develop therapies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are focused on the interaction between the spike protein, which decorates the surface of the virus, and its host receptor, human angiotensin-converting enzyme 2 (hACE2). Linsky et al. describe a de novo design strategy that allowed them to engineer decoy proteins that bind to the spike protein by replicating the hACE2 interface. The best decoy, CTC-445, bound with low nanomolar affinity, and selection of viral mutants that decrease binding is unlikely because this would also affect binding to hACE2. A bivalent version of CTC-445 bound even more tightly, neutralized SARS-CoV-2 infection of cells, and protected hamsters from a SARS-CoV-2 challenge. The stable decoy has the potential for respiratory therapeutic delivery. Science , this issue p. 1208

Funder

National Institutes of Health

National Institute of Allergy and Infectious Diseases

Georgia Research Alliance

Neoleukin

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference67 articles.

1. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

2. Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases