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A 3D structural SARS-CoV-2-human interactome to explore genetic and drug perturbations.
Wierbowski, Shayne D; Liang, Siqi; Liu, Yuan; Chen, You; Gupta, Shagun; Andre, Nicole M; Lipkin, Steven M; Whittaker, Gary R; Yu, Haiyuan.
  • Wierbowski SD; Department of Computational Biology, Cornell University, Ithaca, NY, USA.
  • Liang S; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
  • Liu Y; Department of Computational Biology, Cornell University, Ithaca, NY, USA.
  • Chen Y; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
  • Gupta S; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
  • Andre NM; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
  • Lipkin SM; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
  • Whittaker GR; Department of Computational Biology, Cornell University, Ithaca, NY, USA.
  • Yu H; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
Nat Methods ; 18(12): 1477-1488, 2021 12.
Article in English | MEDLINE | ID: covidwho-1541247
ABSTRACT
Emergence of new viral agents is driven by evolution of interactions between viral proteins and host targets. For instance, increased infectivity of SARS-CoV-2 compared to SARS-CoV-1 arose in part through rapid evolution along the interface between the spike protein and its human receptor ACE2, leading to increased binding affinity. To facilitate broader exploration of how pathogen-host interactions might impact transmission and virulence in the ongoing COVID-19 pandemic, we performed state-of-the-art interface prediction followed by molecular docking to construct a three-dimensional structural interactome between SARS-CoV-2 and human. We additionally carried out downstream meta-analyses to investigate enrichment of sequence divergence between SARS-CoV-1 and SARS-CoV-2 or human population variants along viral-human protein-interaction interfaces, predict changes in binding affinity by these mutations/variants and further prioritize drug repurposing candidates predicted to competitively bind human targets. We believe this resource ( http//3D-SARS2.yulab.org ) will aid in development and testing of informed hypotheses for SARS-CoV-2 etiology and treatments.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Attachment / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Type of study: Etiology study / Prognostic study / Reviews Topics: Variants Limits: Humans Language: English Journal: Nat Methods Journal subject: Laboratory Techniques and procedures Year: 2021 Document Type: Article Affiliation country: S41592-021-01318-w

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Attachment / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Type of study: Etiology study / Prognostic study / Reviews Topics: Variants Limits: Humans Language: English Journal: Nat Methods Journal subject: Laboratory Techniques and procedures Year: 2021 Document Type: Article Affiliation country: S41592-021-01318-w