A 3D structural SARS-CoV-2-human interactome to explore genetic and drug perturbations. Academic Article uri icon

Overview

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.

publication date

  • November 29, 2021

Research

keywords

  • Angiotensin-Converting Enzyme 2
  • COVID-19
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus
  • Virus Attachment

Identity

PubMed Central ID

  • PMC8665054

Scopus Document Identifier

  • 85120031949

Digital Object Identifier (DOI)

  • 10.1038/s41592-021-01318-w

PubMed ID

  • 34845387

Additional Document Info

volume

  • 18

issue

  • 12