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