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SARS-CoV2 (COVID-19) Structural/Evolution Dynamicome: Insights into functional evolution and human genomics.
bioRxiv. 2020 May 15B

Abstract

The SARS-CoV-2 pandemic, starting in 2019, has challenged the speed at which labs perform science, ranging from discoveries of the viral composition to handling health outcomes in humans. The small ~30kb single-stranded RNA genome of Coronaviruses makes them adept at cross species spread and drift, increasing their probability to cause pandemics. However, this small genome also allows for a robust understanding of all proteins coded by the virus. We employed protein modeling, molecular dynamic simulations, evolutionary mapping, and 3D printing to gain a full proteome and dynamicome understanding of SARS-CoV-2. The Viral Integrated Structural Evolution Dynamic Database (VIStEDD) has been established (prokoplab.com/vistedd), opening future discoveries and educational usage. In this paper, we highlight VIStEDD usage for nsp6, Nucleocapsid (N), and Spike (S) surface glycoprotein. For both nsp6 and N we reveal highly conserved surface amino acids that likely drive protein-protein interactions. In characterizing viral S protein, we have developed a quantitative dynamics cross correlation matrix insight into interaction with the ACE2/SLC6A19 dimer complex. From this quantitative matrix, we elucidated 47 potential functional missense variants from population genomic databases within ACE2/SLC6A19/TMPRSS2, warranting genomic enrichment analyses in SARS-CoV-2 patients. Moreover, these variants have ultralow frequency, but can exist as hemizygous in males for ACE2, which falls on the X-chromosome. Two noncoding variants (rs4646118 and rs143185769) found in ~9% of African descent individuals for ACE2 may regulate expression and be related to increased susceptibility of African Americans to SARS-CoV-2. This powerful database of SARS-CoV-2 can aid in research progress in the ongoing pandemic.

Authors

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Pub Type(s)

Preprint

Language

eng

PubMed ID

32511397

Citation

Gupta, Ruchir, et al. "SARS-CoV2 (COVID-19) Structural/Evolution Dynamicome: Insights Into Functional Evolution and Human Genomics." BioRxiv : the Preprint Server for Biology, 2020.
Gupta R, Charron J, Stenger CL, et al. SARS-CoV2 (COVID-19) Structural/Evolution Dynamicome: Insights into functional evolution and human genomics. bioRxiv : the preprint server for biology. 2020.
Gupta, R., Charron, J., Stenger, C. L., Painter, J., Steward, H., Cook, T. W., Faber, W., Frisch, A., Lind, E., Bauss, J., Li, X., Sirpilla, O., Soehnlen, X., Underwood, A., Hinds, D., Morris, M., Lamb, N., Carcillo, J. A., Bupp, C., ... Prokop, J. W. (2020). SARS-CoV2 (COVID-19) Structural/Evolution Dynamicome: Insights into functional evolution and human genomics. BioRxiv : the Preprint Server for Biology. https://doi.org/10.1101/2020.05.15.098616
Gupta R, et al. SARS-CoV2 (COVID-19) Structural/Evolution Dynamicome: Insights Into Functional Evolution and Human Genomics. bioRxiv : the preprint server for biology. 2020 May 15; PubMed PMID: 32511397.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SARS-CoV2 (COVID-19) Structural/Evolution Dynamicome: Insights into functional evolution and human genomics. AU - Gupta,Ruchir, AU - Charron,Jacob, AU - Stenger,Cynthia L, AU - Painter,Jared, AU - Steward,Hunter, AU - Cook,Taylor W, AU - Faber,William, AU - Frisch,Austin, AU - Lind,Eric, AU - Bauss,Jacob, AU - Li,Xiaopeng, AU - Sirpilla,Olivia, AU - Soehnlen,Xavier, AU - Underwood,Adam, AU - Hinds,David, AU - Morris,Michele, AU - Lamb,Neil, AU - Carcillo,Joseph A, AU - Bupp,Caleb, AU - Uhal,Bruce D, AU - Rajasekaran,Surender, AU - Prokop,Jeremy W, Y1 - 2020/05/15/ PY - 2020/6/9/entrez PY - 2020/6/9/pubmed PY - 2020/6/9/medline JF - bioRxiv : the preprint server for biology N2 - The SARS-CoV-2 pandemic, starting in 2019, has challenged the speed at which labs perform science, ranging from discoveries of the viral composition to handling health outcomes in humans. The small ~30kb single-stranded RNA genome of Coronaviruses makes them adept at cross species spread and drift, increasing their probability to cause pandemics. However, this small genome also allows for a robust understanding of all proteins coded by the virus. We employed protein modeling, molecular dynamic simulations, evolutionary mapping, and 3D printing to gain a full proteome and dynamicome understanding of SARS-CoV-2. The Viral Integrated Structural Evolution Dynamic Database (VIStEDD) has been established (prokoplab.com/vistedd), opening future discoveries and educational usage. In this paper, we highlight VIStEDD usage for nsp6, Nucleocapsid (N), and Spike (S) surface glycoprotein. For both nsp6 and N we reveal highly conserved surface amino acids that likely drive protein-protein interactions. In characterizing viral S protein, we have developed a quantitative dynamics cross correlation matrix insight into interaction with the ACE2/SLC6A19 dimer complex. From this quantitative matrix, we elucidated 47 potential functional missense variants from population genomic databases within ACE2/SLC6A19/TMPRSS2, warranting genomic enrichment analyses in SARS-CoV-2 patients. Moreover, these variants have ultralow frequency, but can exist as hemizygous in males for ACE2, which falls on the X-chromosome. Two noncoding variants (rs4646118 and rs143185769) found in ~9% of African descent individuals for ACE2 may regulate expression and be related to increased susceptibility of African Americans to SARS-CoV-2. This powerful database of SARS-CoV-2 can aid in research progress in the ongoing pandemic. UR - https://www.unboundmedicine.com/medline/citation/32511397/SARS_CoV2__COVID_19__Structural/Evolution_Dynamicome:_Insights_into_functional_evolution_and_human_genomics_ L2 - https://doi.org/10.1101/2020.05.15.098616 DB - PRIME DP - Unbound Medicine ER -
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