Mutation in spike D614G protein alters SARS-CoV-2 proliferative capacity



A recent publication in the journal Nature reports that the mutation in the spike D614G protein alters the proliferative capacity of SARS-CoV-2.The literature is reviewed by Professors of the National and Kapodistrian University of Athens, Dimitrios Paraskevi ,) and Thanos Dimopoulos (Professor of Therapy and Rector of EKPA). Since the first appearance of the new coronavirus SARS-CoV-2 in China at the end of 2019, more than 43 million documented infections and more than 1 million deaths have been recorded worldwide. The mechanism by which severe disease is caused is not fully understood and the question remains to this day, to what extent does the genetic heterogeneity of the virus, in addition to the host’s immune response, contribute to disease prognosis? Analyzes in more than 28,000 spike gene May 2020 showed that an amino acid mutation p codon 614 (D614G) was rare before March but rates increased significantly during the pandemic, reaching levels of over 74% in the SARS-CoV-2 sequences available by June 2020. This mutation is combined with other mutations. in other areas of the genome. Due to the above data, the reasonable question arises, whether the strains with these mutations have a natural advantage, ie whether they are associated with increased infectivity, or increased chance of serious disease. In the present study, the D641G mutation in the spike region was associated with increased proliferative capacity in upper respiratory tract due to increased infectivity of the virus. Compared with wild-type virus (D614), the mutant virus (G614) was found to have a high proliferative capacity in Calu-3 cells of the lung and in human respiratory tissues. The increased proliferative capacity was associated with increased virus infectivity with the mutation. G614. Higher viral load of G614 strains in the upper airway in patients with COVID-19 and in experimental animals suggests the role of the D614G mutation in virus infectivity. High levels of SARS-CoV-2 viral replication in to be attributed to the higher expression levels of the receptorACE2 in the nasal cavity compared to the lower respiratory tract. Compared to D614, the G614 virus multiplies at higher levels in the upper airway but not in the lungs of experimental animals, suggesting that the D614G mutation may not be conducive to the lungs. Patients infected with G614 virus had higher levels of viral RNA than D614 viruses, but did not develop more severe disease. The model in experimental animals indicates that the G614 virus is more contagious than the D614 virus in nasal lavage and trachea, but not in the lungs, and no differences in weight loss or disease were observed.If the characteristics of the virus found in experimental animals and in the human model can be extended to patients with COVID-19, this translates into ≥ 10-fold increased infectivity of the G614 virus, highlighting the potential for increased transmission and spread. This possibility is further enhanced by the observation that a COVID-19 patient with distinct populations of SARS-CoV-2 in neck swabs and bead samples were transmitted only by the neck stem. Nevertheless, the effect of D614G in combination with the age of the host on SARS-CoV-2 infection, pathogenicity and infectivity is further investigated. The G614 virus showed slightly greater susceptibility to serum neutralization with antibodies derived from D614 virus-infected animals. As current vaccine trials against SARS-CoV-2 are based on the D614 virus, the results of the G614 virus neutralization allay the concern that the D614G mutation may endanger their potential. To answer this question, further research is needed on human sera collected from individuals vaccinated with spike type D614. In conclusion, the D614G mutation has been found to enhance viral replication in the upper respiratory tract as well as its susceptibility to viral neutralization. findings are important to understand the spread of the ongoing COVID-19 pandemic, the potential vaccine development and development of antibody therapy. Future research focuses on studying other emerging mutations, including those appearing in parallel with the SARS-CoV-2 D614G mutation. Follow it on Google News and be the first to know all the news See all the latest News from Greece and the World, at



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