|  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 of a respiratory illness, and was named COVID-19 [1].
A video (by Elara Systems) shows how the virus interacts with its human (host) cell, via its spikes (whose 3D structure was determined in the McLellan Lab[2]), thus permitting the viral genome to enter its host & begin infection.
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.
Potential treatments for COVID-19
- 27-Mar-2020 Science - Not wearing masks to protect against coronavirus is a big mistake, top Chinese scientist, Dr. George Gao, Director General of the Chinese CDC says, as reported in Science.
- 23-Mar-2020 NY Times - A USA, French UK study identified 69 drugs to test against the coronavirus[3]. As reported in the New York Times "The researchers sought drugs that also latch onto the human proteins that the coronavirus seems to need to enter and replicate in human cells."
- A French study[4] showed, despite its small sample size (20 patients treated), that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.
Videos helping to explain COVID-19
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Scientists have turned the coronavirus spike protein structure into music(!!), as reported in Science by Soundcloud.
The Czech Republic took the uncommon step of making wearing of masks mandatory in public spaces, prompting a grassroots effort to make & wear masks. The impact has been extraordinary!!
Japan researchers show how Coronavirus spreads through micro droplets. These tiny droplets containing the virus can stay in the air for extended periods.
Speaking face-to-face is exchanging saliva, so stop speaking face-to-face and stay healthy by stoptheviruscovid.
Modeling an epidemic (6-Mar-2020) We're not ready for the next epidemic by 3blue1brown.
Fighting Coronavirus with Soap by PDB-101.
Background about the Coronavirus-COVID-19 and details of its 3D structure by biolution GmBH.
Outbreak of COVID-19 explained through 3D Medical Animation (Feb 11, 2020) by Sci Animations.
Bill Gates Ted Talk (3-Apr-2015) We're not ready for the next epidemic by Ted Talks.
Jürgen Bosch Presentation (31-Mar-2020) Coronavirus: How it Ticks and What we are Doing to Stop it by Jürgen Bosch.
Useful sites on COVID-19
- A summary of key findings about COVID-19 can be found at CDC.
- Coronavirus Evolved Naturally, and ‘Is Not a Laboratory Construct,’ in a study in Nature Med by Anderson and colleagues [5].
- Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of COVID-19 in China, with some promising results summarized.[6].
- Crowdfight COVID-19 - A scientific crowdsourcing initiative to put all available resources at the service of the fight against COVID-19
- A computer game, developed at the Inst for Protein Design (U Washington), uses crowdsourcing to try to find new lead compound that might become drugs to treat COVID-19.
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.
- Main protease: it is a cysteine protease that is essential for the viral life cycle.
3D structural studies on SARS-CoV-2 virus
- A team of Chinese scientists determined, by Cryo-EM, the coronavirus spike receptor-binding domain complexed with its receptor ACE2 PDB-ID 6LZG. (To be published).
- A team of US and Chinese scientists determined the crystal structure of 2019-nCoV spike receptor-binding domain bound with ACE2 6M0J (To be published).
- A team of US scientists determined, by Cryo-EM, the structure of the SARS-CoV-2 spike glycoprotein (open & closed states) [7], PDB-ID 6VXX & 6VYB
- Crystal structure of SARS-CoV-2 receptor binding domain in complex with human antibody CR3022 6W41 (To be published).
- Crystal Structure of the methyltransferase-stimulatory factor complex of NSP16 and NSP10 from SARS CoV-2 6W61 (To be published).
- Crystal Structure of ADP ribose phosphatase of NSP3 from SARS CoV-2 in complex with AMP 6W6Y (To be published).
- Structure of NSP10 - NSP16 Complex from SARS-CoV-2 6W75 (To be published).
- Crystal structure of SARS-CoV-2 nucleocapsid protein N-terminal RNA binding domain 6M3M (To be published).
- Crystal structure of Nsp9 RNA binding protein of SARS CoV-2 6W4B (To be published).
- Crystal Structure of NSP16 - NSP10 Complex from SARS-CoV-2 6W4H (To be published).
- Cryo-EM structure of the 2019-nCoV RBD/ACE2-B0AT1 complex[8] 6M17.
- Crystal structure of RNA binding domain of nucleocapsid phosphoprotein from SARS coronavirus 2 6VYO (To be published).
- Crystal structure of NSP15 Endoribonuclease from SARS CoV-2 in the Complex with a Citrate 6W01 (To be published).
- Crystal structure of ADP ribose phosphatase of NSP3 from SARS CoV-2 in the complex with ADP ribose 6W02 (To be published).
- Crystal structure of 2019-nCoV chimeric receptor-binding domain complexed with its receptor human ACE2 6VW1 (To be published).
- Crystal structure of NSP15 Endoribonuclease from SARS CoV-2 6VWW (To be published).
- Crystal Structure of ADP ribose phosphatase of NSP3 from SARS CoV-2 6VXS (To be published).
- Crystal structure of the 2019-nCoV HR2 Domain 6LVN (To be published).
- Crystal structure of post fusion core of 2019-nCoV S2 subunit 6LXT (To be published).
- Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors, from the Hilgenfeld lab[9], Apo Struture: PDB-ID 6Y2E, and complexes with inhibitors: PDB-ID 6Y2F and 6Y2G.
- 3D Structure of RNA-dependent RNA polymerase from COVID-19, a major antiviral drug target from the Rao lab in Beijing[10].
- Crystal structure of the Mpro from COVID-19 and discovery of inhibitors in a study by scientists from Shanghai & Beijing [11], PDB-ID 2h2z.
- Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2 in a study by scientists from USA[12], PDB-ID 6w01.
- A study by Zhou & colleagues on the structural basis for the recognition of the SARS-CoV-2 (COVID-19) by full-length human ACE2 gives insights to the molecular basis for coronavirus recognition and infection[13].
- The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. A study by McLellan and colleagues in "Science" on the Cryo-EM structure of the COVID-19 spike protein. This structure should greatly aid in the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis[2], PDB-ID 6vsb.
References
- ↑ Naming the coronavirus disease (COVID-19) and the virus that causes it
- ↑ 2.0 2.1 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
- ↑ Gordon, et al. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing: bioRxiv (online) 2020 http://doi.org/10.1101/2020.03.22.002386
- ↑ Gautret, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open- label non-randomized clinical trial: Intl J Antimcrob Agents (in press) 2020 http://dx.doi.org/10.1016/j.ijantimicag.2020.105949
- ↑ Andersen, et al. The proximal origin of SARS-CoV-2: Nature Med (in press) 2020 http://dx.doi.org/10.1038/s41591-020-0820-9]
- ↑ Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther. 2020;14(1):58-60. doi: 10.5582/ddt.2020.01012. PMID:32147628 doi:http://dx.doi.org/10.5582/ddt.2020.01012
- ↑ 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
- ↑ Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2. Science. 2020 Mar 4. pii: science.abb2762. doi: 10.1126/science.abb2762. PMID:32132184 doi:http://dx.doi.org/10.1126/science.abb2762
- ↑ Zhang L, Lin D, Sun X, Curth U, Drosten C, Sauerhering L, Becker S, Rox K, Hilgenfeld R. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved alpha-ketoamide inhibitors. Science. 2020 Mar 20. pii: science.abb3405. doi: 10.1126/science.abb3405. PMID:32198291 doi:http://dx.doi.org/10.1126/science.abb3405
- ↑ Gao, et al. Structure of RNA-dependent RNA polymerase from 2019-nCoV, a major antiviral drug target: bioRxiv (online) 2020 https://doi.org/10.1101/2020.03.16.993386
- ↑ Jin, et al. Structure of Mpro from COVID-19 virus and discovery of its inhibitors: bioRxiv (online) 2020 http://doi.org/10.1101/2020.02.26.964882
- ↑ Kim, et al. Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2: bioRxiv (online) 2020 http://doi.org/10.1101/2020.03.02.968388
- ↑ Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2. Science. 2020 Mar 4. pii: science.abb2762. doi: 10.1126/science.abb2762. PMID:32132184 doi:http://dx.doi.org/10.1126/science.abb2762
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