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SARS-CoV-2 (COVID-19) structural and evolutionary dynamicome: Insights into functional evolution and human genomics.
| Content Provider | Europe PMC |
|---|---|
| Author | Gupta, Ruchir Charron, Jacob Stenger, Cynthia L. Painter, Jared Steward, Hunter Cook, Taylor W. Faber, William Frisch, Austin Lind, Eric Bauss, Jacob Li, Xiaopeng Sirpilla, Olivia Soehnlen, Xavier Underwood, Adam Hinds, David Morris, Michele Lamb, Neil Carcillo, Joseph A. Bupp, Caleb Uhal, Bruce D. Rajasekaran, Surender Prokop, Jeremy W. |
| Copyright Year | 2020 |
| Abstract | The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has challenged the speed at which laboratories can discover the viral composition and study health outcomes. The small ∼30-kb ssRNA genome of coronaviruses makes them adept at cross-species spread while enabling a robust understanding of all of the proteins the viral genome encodes. We have employed protein modeling, molecular dynamics simulations, evolutionary mapping, and 3D printing to gain a full proteome- and dynamicome-level understanding of SARS-CoV-2. We established the Viral Integrated Structural Evolution Dynamic Database (VIStEDD at RRID:SCR_018793) to facilitate future discoveries and educational use. Here, we highlight the use of VIStEDD for nsp6, nucleocapsid (N), and spike (S) surface glycoprotein. For both nsp6 and N, we found highly conserved surface amino acids that likely drive protein–protein interactions. In characterizing viral S protein, we developed a quantitative dynamics cross-correlation matrix to gain insights into its interactions with the angiotensin I–converting enzyme 2 (ACE2)–solute carrier family 6 member 19 (SLC6A19) dimer. Using this quantitative matrix, we elucidated 47 potential functional missense variants from genomic databases within ACE2/SLC6A19/transmembrane serine protease 2 (TMPRSS2), warranting genomic enrichment analyses in SARS-CoV-2 patients. These variants had ultralow frequency but existed in males hemizygous for ACE2. Two ACE2 noncoding variants (rs4646118 and rs143185769) present in ∼9% of individuals of African descent may regulate ACE2 expression and may be associated with increased susceptibility of African Americans to SARS-CoV-2. We propose that this SARS-CoV-2 database may aid research into the ongoing pandemic. |
| ISSN | 00219258 |
| Volume Number | 295 |
| PubMed Central reference number | PMC7450099 |
| Issue Number | 33 |
| PubMed reference number | 32587094 |
| Journal | The Journal of Biological Chemistry [J. Biol. Chem] |
| e-ISSN | 1083351X |
| DOI | 10.1074/jbc.RA120.014873 |
| Language | English |
| Publisher | Gupta et al. |
| Publisher Date | 2020-06-25 |
| Access Restriction | Open |
| Rights License | Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. © 2020 © 2020 Gupta et al. |
| Subject Keyword | molecular dynamics molecular evolution human genetics RNA virus virus entry protein structure receptor structure-function post-translational modification (PTM) COVID-19 severe acute respiratory coronavirus 2 (SARS-CoV-2) |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology Biochemistry |
