File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

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

TitleDe novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2
Authors
Issue Date2020
PublisherAmerican Association for the Advancement of Science. The Journal's web site is located at http://sciencemag.org
Citation
Science, 2020, v. 370 n. 6521, p. 1208-1214 How to Cite?
AbstractWe developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins to infect the cell. Our pipeline allowed the design, validation, and optimization of de novo human angiotensin-converting enzyme 2 (hACE2) decoys to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The best monovalent decoy, CTC-445.2, bound with low nanomolar affinity and high specificity to the receptor-binding domain (RBD) of the spike protein. Cryo–electron microscopy (cryo-EM) showed that the design is accurate and can simultaneously bind to all three RBDs of a single spike protein. Because the decoy replicates the spike protein target interface in hACE2, it is intrinsically resilient to viral mutational escape. A bivalent decoy, CTC-445.2d, showed ~10-fold improvement in binding. CTC-445.2d potently neutralized SARS-CoV-2 infection of cells in vitro, and a single intranasal prophylactic dose of decoy protected Syrian hamsters from a subsequent lethal SARS-CoV-2 challenge.
Persistent Identifierhttp://hdl.handle.net/10722/304479
ISSN
2020 Impact Factor: 47.728
2020 SCImago Journal Rankings: 12.556
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLinsky, TW-
dc.contributor.authorVergara, R-
dc.contributor.authorCodina, N-
dc.contributor.authorNelson, JW-
dc.contributor.authorWalker, MJ-
dc.contributor.authorSu, W-
dc.contributor.authorBarnes, CO-
dc.contributor.authorHsiang, TY-
dc.contributor.authorEsser-Nobis, K-
dc.contributor.authorYu, K-
dc.contributor.authorReneer, ZB-
dc.contributor.authorHou, YJ-
dc.contributor.authorPriya, T-
dc.contributor.authorMitsumoto, M-
dc.contributor.authorPong, A-
dc.contributor.authorLau, UY-
dc.contributor.authorMason, ML-
dc.contributor.authorChen, J-
dc.contributor.authorChen, A-
dc.contributor.authorBerrocal, T-
dc.contributor.authorPeng, H-
dc.contributor.authorClairmont, NS-
dc.contributor.authorCastellanos, J-
dc.contributor.authorLin, YR-
dc.contributor.authorJosephson-Day, A-
dc.contributor.authorBaric, RS-
dc.contributor.authorFuller, DH-
dc.contributor.authorWalkey, CD-
dc.contributor.authorRoss, TM-
dc.contributor.authorSwanson, R-
dc.contributor.authorBjorkman, PJ-
dc.contributor.authorGale, M-
dc.contributor.authorBlancas-Mejia, LM-
dc.contributor.authorYen, HL-
dc.contributor.authorSilva, DA-
dc.date.accessioned2021-09-23T09:00:36Z-
dc.date.available2021-09-23T09:00:36Z-
dc.date.issued2020-
dc.identifier.citationScience, 2020, v. 370 n. 6521, p. 1208-1214-
dc.identifier.issn0036-8075-
dc.identifier.urihttp://hdl.handle.net/10722/304479-
dc.description.abstractWe developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins to infect the cell. Our pipeline allowed the design, validation, and optimization of de novo human angiotensin-converting enzyme 2 (hACE2) decoys to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The best monovalent decoy, CTC-445.2, bound with low nanomolar affinity and high specificity to the receptor-binding domain (RBD) of the spike protein. Cryo–electron microscopy (cryo-EM) showed that the design is accurate and can simultaneously bind to all three RBDs of a single spike protein. Because the decoy replicates the spike protein target interface in hACE2, it is intrinsically resilient to viral mutational escape. A bivalent decoy, CTC-445.2d, showed ~10-fold improvement in binding. CTC-445.2d potently neutralized SARS-CoV-2 infection of cells in vitro, and a single intranasal prophylactic dose of decoy protected Syrian hamsters from a subsequent lethal SARS-CoV-2 challenge.-
dc.languageeng-
dc.publisherAmerican Association for the Advancement of Science. The Journal's web site is located at http://sciencemag.org-
dc.relation.ispartofScience-
dc.rightsScience. Copyright © American Association for the Advancement of Science.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleDe novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2-
dc.typeArticle-
dc.identifier.emailSu, W: suwen@hku.hk-
dc.identifier.emailYen, HL: hyen@hku.hk-
dc.identifier.authorityYen, HL=rp00304-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1126/science.abe0075-
dc.identifier.pmid33154107-
dc.identifier.pmcidPMC7920261-
dc.identifier.hkuros325617-
dc.identifier.volume370-
dc.identifier.issue6521-
dc.identifier.spage1208-
dc.identifier.epage1214-
dc.identifier.isiWOS:000596071300060-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats