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Related Experiment Video

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Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells

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SARS-CoV2 (COVID-19) Structural/Evolution Dynamicome: Insights into functional evolution and human genomics.

Ruchir Gupta, Jacob Charron, Cynthia L Stenger

Biorxiv : the Preprint Server for Biology

|June 9, 2020

Summary

Scientists created the Viral Integrated Structural Evolution Dynamic Database (VIStEDD) to understand SARS-CoV-2 proteins. This resource aids research into viral dynamics and potential human genetic links to COVID-19 susceptibility.

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Area of Science:

Virology
Structural Biology
Genomics

Background:

The SARS-CoV-2 pandemic highlighted the need for rapid scientific understanding of viral mechanisms.
Coronaviruses' small RNA genomes facilitate rapid evolution and cross-species transmission, necessitating detailed proteomic and dynamic analyses.

Approach:

Utilized protein modeling, molecular dynamics simulations, and evolutionary mapping to create the Viral Integrated Structural Evolution Dynamic Database (VIStEDD).
Developed a quantitative dynamics cross-correlation matrix to analyze the interaction between the SARS-CoV-2 Spike (S) protein and the ACE2/SLC6A19 dimer complex.
Integrated population genomic data to identify potential functional variants in host-pathogen interaction proteins.

Key Points:

VIStEDD provides a comprehensive proteome and dynamicome understanding of SARS-CoV-2, with specific insights into nsp6, Nucleocapsid (N), and Spike (S) proteins.
Identified highly conserved surface amino acids in nsp6 and N proteins, suggesting crucial roles in protein-protein interactions.
Elucidated 47 potential functional missense variants in ACE2, SLC6A19, and TMPRSS2, with particular attention to variants potentially affecting ACE2 expression in individuals of African descent.

Conclusions:

VIStEDD serves as a valuable resource for future SARS-CoV-2 research and education.
Identified host genetic variants, including specific ACE2 noncoding variants, that may influence COVID-19 susceptibility, particularly in certain populations.
The study underscores the importance of integrating structural dynamics, evolutionary analysis, and population genomics for a deeper understanding of viral pandemics.