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Molecular determinants and mechanism for antibody cocktail preventing SARS-CoV-2 escape.
Ku, Zhiqiang; Xie, Xuping; Davidson, Edgar; Ye, Xiaohua; Su, Hang; Menachery, Vineet D; Li, Yize; Yuan, Zihao; Zhang, Xianwen; Muruato, Antonio E; I Escuer, Ariadna Grinyo; Tyrell, Breanna; Doolan, Kyle; Doranz, Benjamin J; Wrapp, Daniel; Bates, Paul F; McLellan, Jason S; Weiss, Susan R; Zhang, Ningyan; Shi, Pei-Yong; An, Zhiqiang.
  • Ku Z; Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
  • Xie X; Department of Biochemistry and Molecular Biology, Institute for Human Infection and Immunity, Sealy Institute for Vaccine Sciences, Sealy Center for Structural Biology & Molecular Biophysics, Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, U
  • Davidson E; Integral Molecular, Philadelphia, Pennsylvania, PA, 19104, USA.
  • Ye X; Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
  • Su H; Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
  • Menachery VD; Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
  • Li Y; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Yuan Z; Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
  • Zhang X; Department of Biochemistry and Molecular Biology, Institute for Human Infection and Immunity, Sealy Institute for Vaccine Sciences, Sealy Center for Structural Biology & Molecular Biophysics, Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, U
  • Muruato AE; Department of Biochemistry and Molecular Biology, Institute for Human Infection and Immunity, Sealy Institute for Vaccine Sciences, Sealy Center for Structural Biology & Molecular Biophysics, Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, U
  • I Escuer AG; Integral Molecular, Philadelphia, Pennsylvania, PA, 19104, USA.
  • Tyrell B; Integral Molecular, Philadelphia, Pennsylvania, PA, 19104, USA.
  • Doolan K; Integral Molecular, Philadelphia, Pennsylvania, PA, 19104, USA.
  • Doranz BJ; Integral Molecular, Philadelphia, Pennsylvania, PA, 19104, USA.
  • Wrapp D; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, 78712, USA.
  • Bates PF; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • McLellan JS; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, 78712, USA.
  • Weiss SR; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Zhang N; Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA. Ningyan.Zhang@uth.tmc.edu.
  • Shi PY; Department of Biochemistry and Molecular Biology, Institute for Human Infection and Immunity, Sealy Institute for Vaccine Sciences, Sealy Center for Structural Biology & Molecular Biophysics, Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, U
  • An Z; Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA. Zhiqiang.An@uth.tmc.edu.
Nat Commun ; 12(1): 469, 2021 01 20.
Article in English | MEDLINE | ID: covidwho-1039642
ABSTRACT
Antibody cocktails represent a promising approach to prevent SARS-CoV-2 escape. The determinants for selecting antibody combinations and the mechanism that antibody cocktails prevent viral escape remain unclear. We compared the critical residues in the receptor-binding domain (RBD) used by multiple neutralizing antibodies and cocktails and identified a combination of two antibodies CoV2-06 and CoV2-14 for preventing viral escape. The two antibodies simultaneously bind to non-overlapping epitopes and independently compete for receptor binding. SARS-CoV-2 rapidly escapes from individual antibodies by generating resistant mutations in vitro, but it doesn't escape from the cocktail due to stronger mutational constraints on RBD-ACE2 interaction and RBD protein folding requirements. We also identified a conserved neutralizing epitope shared between SARS-CoV-2 and SARS-CoV for antibody CoV2-12. Treatments with CoV2-06 and CoV2-14 individually and in combination confer protection in mice. These findings provide insights for rational selection and mechanistic understanding of antibody cocktails as candidates for treating COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment / Antibodies, Monoclonal Limits: Animals / Female / Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-020-20789-7

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment / Antibodies, Monoclonal Limits: Animals / Female / Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-020-20789-7