Coronavirus Disease 2019 (COVID-19)

SARS-CoV-2 virus. The spikes, that adorn the virus surface, impart a corona like appearance (Fusion Animation).

A novel coronavirus SARS-CoV-2, detected in Wuhan, China in 2019, was found to cause severe respiratory illness named COVID-19^[1].

There’s a new NCBI site on COVID-19/SARS-CoV-2. It will help bench scientists, bioinformaticians, clinicians & others connect with information they need to study SARS-CoV-2 and end the pandemic.

A video (by Elara) shows how the virus interacts with its human (host) cells, via its spike proteins^{[2][3][4][5][6][7]}, thus permitting the viral genome to enter its host & begin infection. The spike protein is induced for optimal binding when it is clipped by a protease (see animation on right side) and more details at SARS-CoV-2_protein_S_activation_by_furin. Subsequently, it undergoes a dramatic transformation to induce membrane fusion and infection, explained with a morph animation at SARS-CoV-2 spike protein fusion transformation.

Useful sites on COVID-19

• A plot of the number of COVID-19 deaths per million people as reported at the Johns Hopkins Web Site, Surprisingly, Israel and USA have the highest numbers.
  

COVID-19 deaths per million peopled)^[8]

• Up to date statistics on Coronavirus cases world-wide at worldometer

• A summary of key findings about COVID-19 can be found at the CDC.

• A series of fascinating COVID-19 Videos.

• COVID-19 AlphaFold2 Models that have been of structures of SARS CoV-2 proteins whose structure have not yet been experimentally determined.

• 3D structural studies on SARS-CoV-2

Potential treatments for COVID-19

• COVID-19: What are our therapeutic options? - Slides courtesy of Prof. Mamta K. Jain, MD, MPH, UT Southwestern Medical Center.

• An int'l group of scientists (UK, Israel & USA) are trying to combat COVID-19 via a massive crystal-based fragment screen. They determined 3D structures of over 90 fragments with 66 in the active site. Details are available at the Diamond Light Source. Contributions are welcome in many different forms PostEra.

• 31-Mar-2020 NY Times C.D.C. Weighs Advising Everyone to Wear a Mask.

SARS-CoV-2 virus proteins

The genome of the SARS-CoV-2 virus codes for 28 proteins: Out of those, 19 have already been characterized structurally.
Details of the 3D structure & function of the key proteins & RNA inside the virus can be seen in the NY Times Bad News Wrapped in Protein: Inside the Coronavirus Genome.

• Main protease: it is a cysteine protease that is essential for the viral life cycle.
• NSP1: Host translation inhibitor nsp1. Inhibits host translation by interacting with the 40S ribosomal subunit.
• NSP2: Non-structural protein 2.
• Papain-like proteinase
• NSP4: Non-structural protein 4.
• Proteinase 3CL-PRO
• AlphaFold2 Theoretical Model NSP6: Non-structural protein 6.
• NSP7: Non-structural protein 7.
• NSP8: Non-structural protein 8.
• NSP9: Non-structural protein 9.
• NSP10: Non-structural protein 10.
• RNA-directed RNA polymerase (RdRp)
• Helicase (Hel): Multi-functional protein with a zinc-binding domain in N-terminus
• Guanine-N7 methyltransferase (ExoN)
• Uridylate-specific endoribonuclease (NendoU)
• 2'-O-methyltransferase (2'-O-MT): Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs.
• Surface glycoprotein (S) and SARS-CoV-2 protein S priming by furin
• ORF3a: Forms homotetrameric potassium sensitive ion channels (viroporin) and may modulate virus release.
• Protein E: Plays a central role in virus morphogenesis and assembly.
• AlphaFold2 Theoretical Model Protein M: Component of the viral envelope.
• ORF6: Could be a determinant of virus virulence.
• ORF7a: Non-structural protein which is dispensable for virus replication in cell culture.
• ORF8: Open Reading Frame 8.
• AlphaFold2 Theoretical Model Protein N: Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP).
• AlphaFold2 Theoretical Model ORF10‎: It is currently unclear whether this region translates into a functional protein.

References

1. ↑ Naming the coronavirus disease (COVID-19) and the virus that causes it
2. ↑ Pillay TS. Gene of the month: the 2019-nCoV/SARS-CoV-2 novel coronavirus spike protein. J Clin Pathol. 2020 Jul;73(7):366-369. doi: 10.1136/jclinpath-2020-206658. Epub, 2020 May 6. PMID:32376714 doi:http://dx.doi.org/10.1136/jclinpath-2020-206658
3. ↑ Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, Graham BS, McLellan JS. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020 Feb 19. pii: science.abb2507. doi: 10.1126/science.abb2507. PMID:32075877 doi:http://dx.doi.org/10.1126/science.abb2507
4. ↑ Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020 Mar 6. pii: S0092-8674(20)30262-2. doi: 10.1016/j.cell.2020.02.058. PMID:32155444 doi:http://dx.doi.org/10.1016/j.cell.2020.02.058
5. ↑ Wrobel AG, Benton DJ, Xu P, Roustan C, Martin SR, Rosenthal PB, Skehel JJ, Gamblin SJ. SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects. Nat Struct Mol Biol. 2020 Jul 9. pii: 10.1038/s41594-020-0468-7. doi:, 10.1038/s41594-020-0468-7. PMID:32647346 doi:http://dx.doi.org/10.1038/s41594-020-0468-7
6. ↑ Thomas G. Furin at the cutting edge: from protein traffic to embryogenesis and disease. Nat Rev Mol Cell Biol. 2002 Oct;3(10):753-66. doi: 10.1038/nrm934. PMID:12360192 doi:http://dx.doi.org/10.1038/nrm934
7. ↑ Wang Q, Zhang Y, Wu L, Niu S, Song C, Zhang Z, Lu G, Qiao C, Hu Y, Yuen KY, Wang Q, Zhou H, Yan J, Qi J. Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2. Cell. 2020 Apr 7. pii: S0092-8674(20)30338-X. doi: 10.1016/j.cell.2020.03.045. PMID:32275855 doi:http://dx.doi.org/10.1016/j.cell.2020.03.045
8. ↑ JHU COVID-19 Web Site https://ourworldindata.org/grapher/weekly-covid-deaths-per-million-people