Cell: In the pandemic, the new coronavirus D614G is generally mutated, and the infection titer has increased by nearly 10 times!

As of July 4, 2020, novel coronavirus pneumonia (Covid-19) cases were diagnosed worldwide, and more than 11 million 200 thousand cases were diagnosed, and the total number of deaths was over 520 thousand.previous studies have shown that antigenic drift can lead to gradual accumulation of influenza virus mutations in the influenza season, and the persistence of the virus pandemic may lead to the accumulation of immune related mutations in the population.although there is no evidence of sars-cov-2 antigen drift, with the extension of human to human transmission time, sars-cov-2 mutation with adaptive advantage and immune resistance may also be obtained.on July 3, 2020, the research team from Duke Human Vaccine Institute, Department of surgery and Los Alamos National Laboratory published the latest research results on mutation in sars-cov-2 pandemic in cell. It was found that sars-cov-2 variant carrying spike protein d614g has become the most common strain in the global pandemic, with adaptability advantages and in many places There was a recurrence pattern.g614 variant has higher titer, and g614 can lead to higher viral load of upper respiratory tract in infected individuals, but it is not related to the severity of the disease.the researchers analyzed sars-cov-2 mutations in the covid 19 pandemic based on regularly updated data from the gisaid SARS cov-2 sequence database.a total of 28576 sequences of spike were compared, and the threshold of spike mutation was set low. It was found that the overall evolution rate of sars-cov-2 was very low, and the amino acid variant d614g was screened out from it.the global transition from the original d614 form to the g614 variant, the amino acid change of spike d614g was caused by a to G nucleotide mutation at position 23403 in Wuhan reference strain. The change of d614g was almost always accompanied by three other mutations: C-T mutation of 5'UTR in 241, C-T silent mutation in 3037, and C-T mutation in 14408.two statistical methods have been developed to assess the increasing frequency of g614 variants. The haplotype containing these four genetic linkage mutations has now become the dominant strain in the global SARS cov-2 epidemic, with mutations starting in Europe, followed by North America and Oceania, and then Asia.d614g 4 haplotype was first detected in Italy on February 20.d614 is located on the surface of spike protein protomer and forms contact with adjacent protomers.freeze electron microscopy showed that the side chains of the neighboring protomers d614 and t859 formed a hydrogen bond between the protomers, which combined the residues of S1 unit of one protomer with that of S2 unit of another.however, g614 will eliminate the hydrogen bond of the side chain, which may increase the flexibility of the main chain and change the interaction between the protomers.in addition, this mutation may regulate the glycosylation of the nearby n616 site and affect the kinetics of the fusion peptide in the space near the protomer.structural mapping of amino acid changes and variation clusters in proteins the sars-cov-2 sequences of 999 covid-19 patients from Sheffield teaching hospital were analyzed and correlated with clinical data. G614 was found to be associated with potentially higher viral load in covid-19 patients, but not with disease severity.the infection titers of pseudovesicular stomatitis virus (VSV) and lentivirus particles of d614 and g614 sars-cov2 spike proteins were quantified. For VSV and lentiviral pseudotype, the infection titer of g614 carrying virus was significantly higher than that of d614, about 2.6 – 9.3 times.the researchers also tested whether the d614g mutation could be similarly neutralized by polyclonal antibodies and found that the sera of convalescent patients neutralized the g614 pseudovirus equally or better than those carrying the d614 pseudovirus. this study timely evaluates the evolution of spike during a pandemic to identify evolutionary changes that may be related to the adaptive or antigenic characteristics of the virus to cope with the risk, which is of great significance for ensuring the effectiveness of vaccine and immunotherapy interventions in clinical practice. end reference: [1] tracking changes in sars-cov-2 spike: evidence that d614g increases effect of the covid-19 virus