Coronavirus Disease 2019 (COVID-19)

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<SX viewer='molstar' load='' size='340' side='right' caption='Cryo-EM structure of a single spike that consists of 3 chains, colored green, brown and purple (PDB-ID [[6vsb]]).' scene='83/839266/Automatic_colors_occlusion/1'>
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<StructureSection load='' size='300' side='right' caption='Morph showing the transition of SARS-CoV-2 spike protein from its closed to open conformation induced by proteolytic cleavage, details at [[SARS-CoV-2_spike_protein_priming_by_furin ]]' scene='85/857141/Morph_alpha_carbons_only/4'>
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[[Image:Ezgif.com-video-to-gif 240px 65pc speed.gif|left|240px|thumb|<span style="font-size:100%">SARS-CoV-2 virus. The <span style="color:blue">spikes</span>, that adorn the <span style="color:red">'''virus surface'''</span>, impart a '''''corona''''' like appearance [http://www.drugtargetreview.com/news/57287/3d-visualisation-of-covid-19-surface-released-for-researchers (Fusion Animation)].</span>]]
[[Image:Ezgif.com-video-to-gif 240px 65pc speed.gif|left|240px|thumb|<span style="font-size:100%">SARS-CoV-2 virus. The <span style="color:blue">spikes</span>, that adorn the <span style="color:red">'''virus surface'''</span>, impart a '''''corona''''' like appearance [http://www.drugtargetreview.com/news/57287/3d-visualisation-of-covid-19-surface-released-for-researchers (Fusion Animation)].</span>]]
<span style="font-size:100%">
<span style="font-size:100%">
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A novel coronavirus (SARS-CoV-2) was found to be the cause of a respiratory illness, first detected in Wuhan, China in 2019.
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A novel coronavirus SARS-CoV-2, detected in Wuhan, China in 2019, was found to cause severe respiratory illness named '''''COVID-19'''''<ref>[http://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it Naming the coronavirus disease (COVID-19) and the virus that causes it]</ref> ('''CO'''rona '''VI'''rus '''D'''isease-20'''19''').
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Details of the '''3D structure & function''' of the key proteins & RNA inside the virus can be seen in the NY Times [http://www.nytimes.com/interactive/2020/04/03/science/coronavirus-genome-bad-news-wrapped-in-protein.html ''Bad News Wrapped in Protein: Inside the Coronavirus Genome''].
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There’s a new [http://go.usa.gov/xw9MV 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.
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An '''animation''' (by [http://elarasystems.com Elara Systems)] shows how the virus [http://youtu.be/hwVl_-lnoys '''interacts with its human (host) cell'''], via its spikes (structure determined in the McLellan Lab<ref name="McLellan">PMID:32075877</ref>), thus permitting the viral genome to enter the host & begin infection.
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A video (by [http://elarasystems.com Elara)] shows how the virus [http://youtu.be/hwVl_-lnoys '''interacts with its human (host) cells'''], via its ''spike'' proteins<ref name="Pillay">PMID:32376714</ref><ref name="McLellan">PMID:32075877</ref><ref name="Veesler">PMID:32155444</ref><ref name="wrobel">PMID: 32647346</ref><ref name="thomas">PMID:12360192</ref><ref name="wang-qi">PMID:32275855</ref>, 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]]'''.
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== Potential treatments for COVID-19 ==
 
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* [http://economictimes.indiatimes.com/news/international/world-news/oxford-university-begins-enrolling-over-500-volunteers-for-coronavirus-vaccine-trial/articleshow/74864754.cms?utm_source=contentofinterest&utm_medium=text&utm_campaign=cppst Oxford Univ begins enrolling over 500 volunteers for a '''coronavirus vaccine trial'''] also see more at [http://www.jenner.ac.uk '''The Jenner Inst'''].
 
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* An international group of scientists are trying to combat COVID-19 via a massive crystal-based 3D fragment screen. They have determined the 3D structures of [http://www.diamond.ac.uk/covid-19/for-scientists/Main-protease-structure-and-XChem/Downloads.html '''over 90 fragments, 66 of which are in the active site''']. All the experimental details and results are available [http://www.diamond.ac.uk/covid-19/for-scientists/Main-protease-structure-and-XChem.html '''online at the Diamond Light Source''']. They welcome contributions in many different forms, see details [http://covid.postera.ai/covid '''PostEra'''].
 
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* 31-Mar-2020 ''NY Times'' [http://www.nytimes.com/2020/03/31/health/cdc-masks-coronavirus.html C.D.C. Weighs Advising Everyone to Wear a Mask].
 
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* 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 [http://www.sciencemag.org/news/2020/03/not-wearing-masks-protect-against-coronavirus-big-mistake-top-chinese-scientist-says ''Science''].
 
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* 23-Mar-2020 ''NY Times'' - A USA, French UK study '''identified 69 drugs to test against the coronavirus'''<ref> 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 http://doi.org/10.1101/2020.03.22.002386]</ref>. As reported in the [http://www.nytimes.com/2020/03/22/science/coronavirus-drugs-chloroquine.html?action=click&module=Top%20Stories&pgtype=Homepage ''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."
 
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* 20-Mar-2020 - Analysis by Abby Olena in ''The Scientist'' on [http://www.the-scientist.com/news-opinion/remdesivir-works-great-against-coronaviruses-in-the-lab-67298?utm_campaign=TS_OTC_2020&utm_source=hs_email&utm_medium=email&utm_content=85306117&_hsenc=p2ANqtz--t49MmUS_nL_8CL8wosEbymFBDq_4smPhI1pSJmSKWA0bURCpjoMb1eYxIVv30SDzsuiNd9PRGTPC30x-gelTGjK-9r9wPWaMjEZIqjaz5Y0tgW5w&_hsmi=85306117 '''Remdesivir Works Against Coronaviruses in the Lab''']
 
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* 20-Mar-2020 - Analysis by Chris Baraniuk in ''The Scientist'' on [http://www.the-scientist.com/news-opinion/is-hype-over-chloroquine-as-a-potential-covid-19-therapy-justified--67301?utm_campaign=TS_OTC_2020&utm_source=hs_email&utm_medium=email&utm_content=85306117&_hsenc=p2ANqtz--t49MmUS_nL_8CL8wosEbymFBDq_4smPhI1pSJmSKWA0bURCpjoMb1eYxIVv30SDzsuiNd9PRGTPC30x-gelTGjK-9r9wPWaMjEZIqjaz5Y0tgW5w&_hsmi=85306117 '''Chloroquine for COVID-19: Cutting Through the Hype''']
 
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* A French study<ref> 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 http://dx.doi.org/10.1016/j.ijantimicag.2020.105949]</ref> 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.
 
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== Movies helping to explain COVID-19 ==
 
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<html5media height="163" width="290">http://www.youtube.com/watch?v=HhNo_IOPOtU</html5media><br>
 
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The Czech Republic took the uncommon step of '''making wearing of masks mandatory in public spaces''', prompting a grassroots [http://www.sciencemag.org/news/2020/03/would-everyone-wearing-face-masks-help-us-slow-pandemicdrive effort to make & wear masks]. '''The impact has been extraordinary!!'''<br>
 
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<html5media height="163" width="290">http://www.youtube.com/watch?v=hm7BmIJrLZE</html5media><br>
 
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Japan researchers show how '''Coronavirus spreads through micro droplets'''. These tiny droplets containing the virus can stay in the air for extended periods.<br>
 
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<html5media height="163" width="290">http://www.youtube.com/watch?v=qzARpgx8cvE</html5media><br>
 
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Speaking face-to-face is exchanging saliva, so '''stop speaking face-to-face and stay healthy''' by [http://stoptheviruscovid19.github.io '''stoptheviruscovid'''].<br>
 
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<html5media height="163" width="290">http://www.youtube.com/watch?v=Kas0tIxDvrg</html5media><br>
 
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Modeling an epidemic (6-Mar-2020) '''''We're not ready for the next epidemic''''' by [http://3b1b.co/covid-thanks '''3blue1brown'''].<br>
 
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<html5media height="163" width="290">https://www.youtube.com/watch?v=s2EVlqql_f8</html5media><br>
 
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'''Fighting Coronavirus with Soap''' by [http://pdb101.rcsb.org/ '''PDB-101'''].<br>
 
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<html5media height="163" width="290">https://www.youtube.com/watch?v=I0TmBsHaGmI</html5media><br>
 
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'''Background about the Coronavirus-COVID-19 and details of its 3D structure''' by [http://www.biolution.net biolution '''GmBH'''].<br>
 
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<html5media height="163" width="290">https://www.youtube.com/watch?v=I-Yd-_XIWJg</html5media><br>
 
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'''Outbreak of COVID-19 explained through 3D Medical Animation (Feb 11, 2020)''' by [http://www.scientificanimations.com '''Sci Animations'''].<br>
 
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<html5media height="163" width="290">http://www.youtube.com/watch?v=6Af6b_wyiwI</html5media><br>
 
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'''Bill Gates Ted Talk (3-Apr-2015) ''We're not ready for the next epidemic''''' by [http://www.ted.com/talks '''Ted Talks'''].
 
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<html5media height="163" width="290">https://www.youtube.com/watch?v=B00tJnbktVo&t=204</html5media><br>
 
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'''Jürgen Bosch Presentation (31-Mar-2020) ''Coronavirus: How it Ticks and What we are Doing to Stop it''''' by [http://www.linkedin.com/in/jubosch '''Jürgen Bosch'''].
 
== Useful sites on COVID-19 ==
== Useful sites on COVID-19 ==
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* [http://deepmind.com/research/open-source/computational-predictions-of-protein-structures-associated-with-COVID-19 Computational predictions of 3D protein structures associated with COVID-19] based on the [http://deepmind.com/blog/article/AlphaFold-Using-AI-for-scientific-discovery AI AlphaFold system]. Coordinates of the 3D structures can be download [http://storage.googleapis.com/deepmind-com-v3-datasets/alphafold-covid19/structures_4_3_2020.zip here as a '''zip''' file].
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* A plot of the Biweekly change in confirmed COVID-19 cases throughout the world
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<imagemap>
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Image:Biweekly change in confirmed COVID-19 cases.jpg|500px
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default [https://ourworldindata.org/grapher/biweekly-growth-covid-cases Our World site with the most recent data]
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</imagemap>
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Clicking the above image goes to the [https://ourworldindata.org/grapher/biweekly-growth-covid-cases Our World in Data] site with the most recent data.
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* Up to date statistics on [http://www.worldometers.info/coronavirus/coronavirus-cases/ Coronavirus cases world-wide at worldometer]
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* A summary of key findings about [http://www.cdc.gov/coronavirus/2019-nCoV/lab/index.html COVID-19] can be found at [http://www.cdc.gov/ the '''CDC'''].
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* A summary of key findings about [http://www.cdc.gov/coronavirus/2019-nCoV/lab/index.html COVID-19] can be found at [http://www.cdc.gov/ CDC].
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* A series of fascinating '''[[COVID-19 Videos]]'''.
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* '''Coronavirus Evolved Naturally''', and ‘Is '''Not''' a Laboratory Construct,’ in a study in Nature Med by Anderson and colleagues <ref>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 http://dx.doi.org/10.1038/s41591-020-0820-9]]</ref>.
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* '''[[Potential treatments for COVID-19]]'''.
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* '''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.<ref>PMID:32147628</ref>.
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* '''[[SARS-CoV-2 virus proteins]]''' - Status of all 3D models of SARS-CoV-2 Virus protein structures.
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* [http://crowdfightcovid19.org Crowdfight COVID-19] - A scientific crowdsourcing initiative to put all available resources at the service of the fight against COVID-19
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* '''[[COVID-19 AlphaFold2 Models]]''' that have been of structures of SARS CoV-2 proteins whose structure have not yet been experimentally determined.
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* A computer game, developed at the [http://www.ipd.uw.edu Inst for Protein Design] (U Washington), uses crowdsourcing to try to find new lead compound that might become drugs to treat COVID-19.
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* '''[[3D structural studies on SARS-CoV-2]]''' - Pointers to research on 3D structural studies on SARS-CoV-2 Virus proteins.
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<html5media height="163" width="290" >https://www.youtube.com/watch?v=gGvlNo3nMfw</html5media>
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== 3D structural studies on Coronavirus COVID-19==
 
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* [http://github.com/thorn-lab/coronavirus_structural_task_force Public resource for the structures from beta-coronavirus with a focus on SARS-CoV and SARS-CoV-2]
 
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* A team of UK & Israeli scientists determined the 3D structures of [http://www.diamond.ac.uk/covid-19/for-scientists/Main-protease-structure-and-XChem/Downloads.html '''over 90 fragments, 66 of which are in the active site'']. All the experimental details and results are available [http://www.diamond.ac.uk/covid-19/for-scientists/Main-protease-structure-and-XChem.html '''online at the Diamond Light Source'''].
 
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* A team of Chinese scientists determined, by Cryo-EM, the''' coronavirus spike receptor-binding domain complexed with its receptor ACE2 PDB-ID''' [http://www.rcsb.org/structure/6LZG 6LZG]. (To be published).
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== References ==
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<references/>
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* A team of US and Chinese scientists determined the crystal structure of '''2019-nCoV spike receptor-binding domain bound with ACE2''' [http://www.rcsb.org/structure/6M0J 6M0J] (To be published).
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</StructureSection>
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* A team of US scientists determined, by Cryo-EM, the '''structure of the SARS-CoV-2 spike glycoprotein (open & closed states)''' <ref>PMID:32155444</ref>, PDB-ID [http://www.rcsb.org/structure/6VXX 6VXX] & [http://www.rcsb.org/structure/6VYB 6VYB]
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* Crystal structure of SARS-CoV-2 receptor binding domain in complex with human antibody CR3022 [http://www.rcsb.org/structure/6W41 6W41] (To be published).
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* Crystal Structure of the methyltransferase-stimulatory factor complex of NSP16 and NSP10 from SARS CoV-2 [http://www.rcsb.org/structure/6W61 6W61] (To be published).
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* Crystal Structure of ADP ribose phosphatase of NSP3 from SARS CoV-2 in complex with AMP [http://www.rcsb.org/structure/6W6Y 6W6Y] (To be published).
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* Structure of NSP10 - NSP16 Complex from SARS-CoV-2 [http://www.rcsb.org/structure/6W75 6W75] (To be published).
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* Crystal structure of SARS-CoV-2 nucleocapsid protein N-terminal RNA binding domain [http://www.rcsb.org/structure/6M3M 6M3M] (To be published).
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* Crystal structure of Nsp9 RNA binding protein of SARS CoV-2 [http://www.rcsb.org/structure/6W4B 6W4B] (To be published).
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* Crystal Structure of NSP16 - NSP10 Complex from SARS-CoV-2 [http://www.rcsb.org/structure/6W4H 6W4H] (To be published).
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* Cryo-EM structure of the 2019-nCoV RBD/ACE2-B0AT1 complex<ref>PMID:32132184</ref> [http://www.rcsb.org/structure/6M17 6M17].
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* Crystal structure of RNA binding domain of nucleocapsid phosphoprotein from SARS coronavirus 2 [http://www.rcsb.org/structure/6VYO 6VYO] (To be published).
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* Crystal structure of NSP15 Endoribonuclease from SARS CoV-2 in the Complex with a Citrate [http://www.rcsb.org/structure/6W01 6W01] (To be published).
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* Crystal structure of ADP ribose phosphatase of NSP3 from SARS CoV-2 in the complex with ADP ribose [http://www.rcsb.org/structure/6W02 6W02] (To be published).
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* Crystal structure of 2019-nCoV chimeric receptor-binding domain complexed with its receptor human ACE2 [http://www.rcsb.org/structure/6VW1 6VW1] (To be published).
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* Crystal structure of NSP15 Endoribonuclease from SARS CoV-2 [http://www.rcsb.org/structure/6VWW 6VWW] (To be published).
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* Crystal Structure of ADP ribose phosphatase of NSP3 from SARS CoV-2 [http://www.rcsb.org/structure/6VXS 6VXS] (To be published).
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* Crystal structure of the 2019-nCoV HR2 Domain [http://www.rcsb.org/structure/6LVN 6LVN] (To be published).
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* Crystal structure of post fusion core of 2019-nCoV S2 subunit [http://www.rcsb.org/structure/6LXT 6LXT] (To be published).
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* Crystal structure of '''SARS-CoV-2 main protease''' provides a basis for design of improved α-ketoamide inhibitors, from the Hilgenfeld lab<ref>PMID:32198291</ref>, Apo Struture: PDB-ID [http://www.rcsb.org/structure/6y2e 6Y2E], and complexes with inhibitors: PDB-ID [http://www.rcsb.org/structure/6y2f 6Y2F] and [http://www.rcsb.org/structure/6y2g 6Y2G].
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* 3D Structure of '''RNA-dependent RNA polymerase from COVID-19''', a '''major antiviral drug target''' from the Rao lab in Beijing<ref> 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 https://doi.org/10.1101/2020.03.16.993386]</ref>.
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* Crystal structure of the '''Mpro from COVID-19''' and '''discovery of inhibitors''' in a study by scientists from Shanghai & Beijing <ref> 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 http://doi.org/10.1101/2020.02.26.964882]</ref>, PDB-ID [[2h2z]].
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* Crystal structure of '''Nsp15 endoribonuclease NendoU from SARS-CoV-2''' in a study by scientists from USA<ref> 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 http://doi.org/10.1101/2020.03.02.968388]</ref>, PDB-ID [[6w01]].
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* 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<ref>PMID:32132184</ref>.
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* '''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<ref name="McLellan" />, PDB-ID [[6vsb]].
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[[Category: Coronavirus]]
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[[Category: Covid-19]]
== References ==
== References ==
<references/>
<references/>
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</SX>
 
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[[Category: Coronavirus]]
 
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[[Category: Covid-19]]
 

Current revision

Morph showing the transition of SARS-CoV-2 spike protein from its closed to open conformation induced by proteolytic cleavage, details at SARS-CoV-2_spike_protein_priming_by_furin

Drag the structure with the mouse to rotate

References

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