SARS-CoV-2 z-bo 2020-10-30 414

　　Since December 8, 2019, several cases of pneumonia of unknown etiology have been reported in Wuhan, Hubei Province, China. Most patients work or live near the local Huanan Seafood Wholesale Market. In the early stages of this type of pneumonia, severe acute respiratory infection symptoms appeared, and some patients soon developed acute respiratory distress syndrome (ARDS), acute respiratory failure and other serious complications.

　　On January 7, 2020, the Chinese Center for Disease Control and Prevention (ChinaCDC) identified a new type of coronavirus in the patient's throat swab samples. It was originally named 2019-nCoV by the World Health Organization (WHO). Most patients with 2019-nCoV pneumonia have mild symptoms and a good prognosis. So far, some patients have developed severe pneumonia, pulmonary edema, ARDS or multiple organ failure and death.

　　The new coronavirus SARS-CoV-2 caused Coronavirus Disease (COVID-19) in 2019 and is currently rampant worldwide. Vaccines are an urgent need to control the pandemic. There is currently no human vaccine against SARS-CoV-2, but about 120 candidate vaccines are being developed. SARS-CoV-2 and two other closely related highly pathogenic viruses SARS-CoV and MERS-CoV belong to the β-coronavirus genus of the coronavirus family. SARS-CoV-2 has a 30 kb single-stranded RNA genome. The nucleocapsid protein (N) and the outer membrane composed of membrane protein (M), envelope protein (E) and spike protein (S) cover the genome. Like SARS-CoV, the S protein of SARS-CoV-2 binds to the co-receptor angiotensin-converting enzyme 2 (ACE2) through the receptor binding domain (RBD) and mediates the virus to host cells. Do it. Prior to this, scientists confirmed that SARS-CoV and MERS-CoVBD contain major conformation-dependent neutralizing epitopes and can trigger effective neutralizing antibodies in immunized animals. This is a promising vaccine development.

　　SARS-CoV-2 spike protein (S protein) variant D614G has replaced the ancestral virus in the world, and reached the level of immobilization within a few months.

　　In a new study, researchers at Harvard University School of Medicine, Thermofisher Scientific andegeneron Pharmaceuticals, discovered that D614G is expressed by human lung cells, colon cells and ectopic expression. We found that human ACE2 or ACE2 homologues from a variety of mammals (including Chinese chrysanthemum bats and Malay pangolins) are more infectious than their ancestral viruses on cells that allow the virus to be infected. Have. The relevant research results were published online in Cell Journal on September 15, 2020, with the title "Structural and Functional Analysis0047D614GSARS-CoV-2SpikeProteinVariant". D614G did not change the synthesis, processing or integration of S protein in SARS-CoV-2 virus particles, but the fast dissociation rate reduced the affinity of D614G for ACE2. Evaluation of the S protein trimer by cryo-electron microscopy showed that D614G disrupted the contact between the S protein proprotein and changed the S protein conformation to a state capable of binding to ACE2, which is considered a virus. The method of particle fusion with target cell membrane. Consistent with this more open conformation, the neutralizing effect of antibodies targeting the S protein receptor binding domain (RBD) did not diminish.