Collaborative project for curation biological processes involved in the COVID-19 disease after SARS-Cov-2 infection. It focuses on experimental evidence and plays with improved annotation of complexes and with the Evidence and Conclusion Ontology. The complexes link to EBI's Complex Portal, resulting from a collaboration with that database at the recent online ELIXIR biohackathon. Editing this pathway is (at this moment) coordinated via the wikipathways.slack.com #sarscov2 channel. Additionally, please feel free to add suggestions to the discussion page (see the tab at the top of this page). The large viral Spike protein (S or surface glycoprotein) forms trimers. It interacts with the host's ACE2 receptor to establish binding (Hoffmann et al 2020). There are suggestions for more than one cell entry mechanism, with the evidence for ACE2/TMPRSS2 entry being most clear now. Lack of expression of TMPRSS2 may explain age differences in COVID19 severity. In this mechanism, to enter the virus needs to be primed by the host protease TMPRSS2 that splits the Spike protein into 2 peptides S1 and S2. S1 contains the ACE2 receptor binding site, S2 binds to the host cell membrane which leads to membrane fusion, the start of the uptake process. The ACE2 receptor interaction was also suggested as the start of specific lung-damaging effects. Other human genes that may be involved in alternative cell uptake mechanisms include CTSL and SLC6A19. c4d Host translation inhibitor nsp1 abf db9 d1a d44 ad4 af3 bf9 aa3 aa3 aa3 aa3 e1a aa3 e1a aa3 nsp3 b94 db2 nsp10 RdRp d8e ef8 b94 Helicase nsp14 d8e NendoU 2'-O-methyltransferase aa3 aa3 2'-O-methyltransferase nsp10 nsp3 nsp10 Host translation inhibitor nsp1 e4e e63 f49 RdRp d8e ef8 b94 abf c43 d94 bcc f1b cc7 c43 c43 d44 cc7 a1d c67 b60 f1b c43 e63 f49 f1b bcc d94 d94 c43 f1b cc7 e53 c43 c1f abf f1b af3 dd6 b8f af3 a7a d8f d8f [ECO_0005031] cc7 [ECO_0005031] c43 [ECO_0005031] bcc f00 c43 [ECO_0005033] abf d94 [ECO_0005031] bbb [ECO_0005031] c43 32511376 PubMed The crystal structure of nsp10-nsp16 heterodimer from SARS-CoV-2 in complex with S-adenosylmethionine. bioRxiv 2020 PubMed Preprint: TMPRSS2 and furin are both essential for proteolytic activation and spread of SARS-1 CoV-2 in human airway epithelial cells and provide promising drug targets 10.1101/2020.04.15.042085v1 2020 32132184 PubMed Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2. 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