Several cases of pneumonia of unknown etiology have been reported in Wuhan, Hubei Province, China, since December 8, 2019.Most of the patients worked or lived nearby in the local South China seafood wholesale market.In the early stages of this pneumonia, severe acute respiratory infection develops, and some patients rapidly develop acute respiratory distress syndrome (ARDS), acute respiratory failure, and other serious complications.On January 7, 2020, China Center for Disease Control and Prevention (China CDC) identified a novel Coronavirus from a throat swab sample of a patient. It was originally named 2019-NCOV by WHO.Most patients with 2019-NCOV pneumonia have mild symptoms and good prognosis.So far, some patients have developed severe pneumonia, pulmonary edema, ARDS or multiple organ failure and death.
Novel CoronavirusSARS-COV-2, which led to coronavirus Disease 2019 (COVID-19), is now ona global rampage.Vaccines are an essential response that is urgently needed to contain the pandemic.There is currently no human vaccine against SARS-COV-2, but about 120 vaccine candidates are under development.
Sars-cov-2 and two other highly pathogenic viruses closely related to sarS-COV and MERs-CoV belong to the coronavirus genus of the Coronavirus family.Sars-cov-2 has a 30KB just, single-stranded RNA genome.Its nucleocapsid protein (N) and outer membrane consisting of membrane protein (M), envelope protein (E), and spike protein (S) envelops its genome.
Like SARS-COV, THE S-protein of SARS-COV-2 binds to its common receptor, angiotensin-converting enzyme 2 (ACE2), through the receptor-binding domain (RBD), mediating the entry of the virus into host cells.Previously, scientists had demonstrated that THE RBD of SARS-COV and Mers-CoV contained major conformation-dependent neutralizing epitopes and could induce powerful neutralizing antibodies in immunized animals, making them promising targets for vaccine development.
Sars-cov-2 spike protein (S protein) variant D614G replaced the ancestral virus globally and within a few months reached a point of near immobilization.
In a new study from the university of Massachusetts medical school, Harvard University, the world's science and technology company and regeneration yuan pharmaceutical researchers found D614G in human lung, colon cells and through the ectopic expression of human ACE2 or from a variety of mammals (including Chinese chrysanthemum bat and the malayan pangolin) of ACE2 homologue allow cells infected by the virus, virus is more infectious than its ancestors.The relevant research results were published online at Cell on September 15, 2020, in a paper entitled "Structural and Functional Analysis of the D614G SARS-COv-2 Spike Protein Variant".
D614G did not change the synthesis, processing, or integration of S protein into SARS-COV-2 virus particles, but due to the rapid dissociation rate, D614G had a decreased affinity for ACE2.
The evaluation of the trimer of S protein by cryogenic electron microscopy showed that D614G destroyed the contact between the protomer of S protein, so that the conformation of S protein turned to the state capable of binding ACE2, which was considered as the way for the fusion of virus particles with the target cell membrane.Consistent with this more open conformation, the neutralizing power of antibodies targeting the S protein receptor binding domain (RBD) is not diminished.