| http://purl.uniprot.org/citations/32877502 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32877502 | http://www.w3.org/2000/01/rdf-schema#comment | "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious respiratory virus that can lead to venous/arterial thrombosis, stroke, renal failure, myocardial infarction, thrombocytopenia, and other end-organ damage. Animal models demonstrating end-organ protection in C3-deficient mice and evidence of complement activation in humans have led to the hypothesis that SARS-CoV-2 triggers complement-mediated endothelial damage, but the mechanism is unclear. Here, we demonstrate that the SARS-CoV-2 spike protein (subunit 1 and 2), but not the N protein, directly activates the alternative pathway of complement (APC). Complement-dependent killing using the modified Ham test is blocked by either C5 or factor D inhibition. C3 fragments and C5b-9 are deposited on TF1PIGAnull target cells, and complement factor Bb is increased in the supernatant from spike protein-treated cells. C5 inhibition prevents the accumulation of C5b-9 on cells, but not C3c; however, factor D inhibition prevents both C3c and C5b-9 accumulation. Addition of factor H mitigates the complement attack. In conclusion, SARS-CoV-2 spike proteins convert nonactivator surfaces to activator surfaces by preventing the inactivation of the cell-surface APC convertase. APC activation may explain many of the clinical manifestations (microangiopathy, thrombocytopenia, renal injury, and thrombophilia) of COVID-19 that are also observed in other complement-driven diseases such as atypical hemolytic uremic syndrome and catastrophic antiphospholipid antibody syndrome. C5 inhibition prevents accumulation of C5b-9 in vitro but does not prevent upstream complement activation in response to SARS-CoV-2 spike proteins."xsd:string |
| http://purl.uniprot.org/citations/32877502 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood.2020008248"xsd:string |
| http://purl.uniprot.org/citations/32877502 | http://purl.uniprot.org/core/author | "Chen H."xsd:string |
| http://purl.uniprot.org/citations/32877502 | http://purl.uniprot.org/core/author | "Yu J."xsd:string |
| http://purl.uniprot.org/citations/32877502 | http://purl.uniprot.org/core/author | "Yuan X."xsd:string |
| http://purl.uniprot.org/citations/32877502 | http://purl.uniprot.org/core/author | "Chaturvedi S."xsd:string |
| http://purl.uniprot.org/citations/32877502 | http://purl.uniprot.org/core/author | "Braunstein E.M."xsd:string |
| http://purl.uniprot.org/citations/32877502 | http://purl.uniprot.org/core/author | "Brodsky R.A."xsd:string |
| http://purl.uniprot.org/citations/32877502 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32877502 | http://purl.uniprot.org/core/name | "Blood"xsd:string |
| http://purl.uniprot.org/citations/32877502 | http://purl.uniprot.org/core/pages | "2080-2089"xsd:string |
| http://purl.uniprot.org/citations/32877502 | http://purl.uniprot.org/core/title | "Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is blocked by factor D inhibition."xsd:string |
| http://purl.uniprot.org/citations/32877502 | http://purl.uniprot.org/core/volume | "136"xsd:string |
| http://purl.uniprot.org/citations/32877502 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32877502 |
| http://purl.uniprot.org/citations/32877502 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/32877502 |
| http://purl.uniprot.org/uniprot/#_A6XNE2-mappedCitation-32877502 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32877502 |
| http://purl.uniprot.org/uniprot/#_K7ERG9-mappedCitation-32877502 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32877502 |
| http://purl.uniprot.org/uniprot/#_P00746-mappedCitation-32877502 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32877502 |
| http://purl.uniprot.org/uniprot/#_Q6FHW3-mappedCitation-32877502 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32877502 |
| http://purl.uniprot.org/uniprot/P00746 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/32877502 |
| http://purl.uniprot.org/uniprot/A6XNE2 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/32877502 |
| http://purl.uniprot.org/uniprot/Q6FHW3 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/32877502 |
| http://purl.uniprot.org/uniprot/K7ERG9 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/32877502 |