Emergence of a highly fit SARS-CoV-2 variant


Sarbecoviruses have emerged twice in the 21st century, causing epidemics and epidemics worldwide. The ongoing epidemic of coronovirus disease 2019 (Kovid-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused unprecedented disruption of human society. Since its emergence in December 2019, SARS-CoV-2 has spread worldwide, infecting over 70 million individuals and causing over 1.6 million deaths in early December 2020. Previous studies have clearly shown that pandemic and pandemic RNA viruses may choose to spread. Mutations that alter RNA virus pathogenesis, virility, infectivity, or a combination of these,1 So far this process remains poorly studied among emerging coronaviruses in animals and humans.

SARS-CoV-2 probably emerged from bats, and early strains identified in Wuhan, China, showed limited genetic diversity, suggesting that the virus may have been introduced from a single source.2 Early zoonotic variants of the novel coronovirus SARS-COV that emerged in 2003 affected the receptor-binding domain (RBD) of the spike protein and thereby enhanced virus docking and entry through the human angiotensin-altered-enzyme-2 (HACE2) receptor .3 In contrast, the spike-protein RBD of early SARS-CoV-2 strains was soon shown to interact efficiently with HC2 receptors.2

However, despite the presence of a COV RNA proofreading activity that yields high replication fidelity, genetic epidemic investigations at the end of February, a budding D614G mutation affecting the spike glycoprotein of SARS-CoV-2 strains from southern Europe Identified; This version has since spread rapidly and become the most prevalent genotype worldwide.4 Patients infected with SARS-CoV-2 associated with D614G are more likely to have viral load in the upper respiratory tract than in patients infected with virus strains without mutations, but the severity of the disease is not affected. Pseudotyped virus continuous cell lines with the G614 form of the SARS-CoV-2 spike protein have been reported to exhibit increased infectivity and increased susceptibility to neutralization. Furthermore, structural analyzes have shown that the RBD of the G614 form of the spike protein is more likely to be “open” conformed than the RBD of the parental D614 form, providing a better ability to bind the HACE2 receptor. However, published reports of the isolation of the D614G substitution in an authentic SARS-CoV-2 recombinant live virus are lacking, as are investigations of the effects of mutations for in vivo replication and pathogenesis.

Increased infection of SARS-CoV-2 affecting the spike protein D614G substitution.

A study recently reported by Plant et al.5 Demonstrated that a variant of SARS-CoV-2 results in increased virus infectivity and yield in primary human airway tissue (panel B), and in human lung epithelial cells (panel A) due to the spike protein D614G substitution, And in the upper airway of the hamster (panel C). These data suggest that D614G mutations result in increased transmittance. In addition, serum samples from D614-virus-infected hamsters can neutralize G614 virus from infected cells (panel D), suggesting that SARS-CoV-2 vaccines are all based on the D614 variant of the spike protein. , Will protect against G614 variants of the virus.

In a recent study, Plant et al. Used reverse genetics to recover isogenic recombinant SARS-CoV viruses encoding D614G mutations.5 The G614 variant replicated more efficiently than the D614 variant in culture and in primary human airway epithelial cells.Figure 1A and 1B). Even at the 1: 1, 3: 1, or 9: 1 of D614-to-G614 variant infection ratios, the contemporary G614 strain provoked the paternal D614 strain in primary human airway epithelial cells. The G614 variant also seemed to be more stable than the parental strain, suggesting that increased stability may be associated with increased infectivity, although additional investigation would be required to confirm this finding.

In studies in hamsters infected with the D614 or G614 variants, Plant et al. It has been shown that the contemporary G614 variant replicated high titers in nasal-wash samples immediately after infection and the paternal D614 version (Figure 1c); These findings suggest that increased fitness in a major upper airway compartment potentially associated with increased transmission. The SARS-CoV-2 G614 variant was not a cause of more severe disease in hamsters than paternal stress, a finding that supports the current findings in humans. Kovid-19 vaccines that are currently being evaluated in clinical trials are based on the original D614 paternal Nike sequence; Therefore, the authors used a panel of serum samples to test whether the G614 variant is sensitive to neutralization as an ancestral strain (Figure 1D). Fortunately, the results showed that it was as sensitive to serum samples as the D614 strain and thus feared that it might evade vaccine-elicited immunity.

Plante et al. Has provided evidence for a genetic and molecular basis for the increased fitness of the G614 variant on ancestral strains, providing strong support for its role in facilitating global proliferation. In contrast to variants in the SARS-CoV 2003 pandemic strain, SARS-CoV-2 may indicate new mechanisms that are associated with pandemics that have spread to human populations. In addition to showing the critical importance of blending genetic epidemiological studies with genetic molecular virologic studies to understand and spread the evolution of pandemic viruses, the findings raise important questions about the future evolutionary trajectory of the SARS-CoV-2 G614 variant . These questions are particularly important at a time when environmental pressures, such as expanding herd immunity, vaccine-induced immunity, antiviral therapy, and public health intervention strategies, through selective pressures – may promote virus survival and escape . Will these selective pressures drive antigenic variation, promote virus stability and transmission capacity, alter the virus’s virulence and pathogenesis, or drive SARS-CoV-2 into alternative hosts as extinction or reservoirs? Plante et al. Instead of reactive, SARS-COV-2 and other potential emerging clear an important requirement for proactive rather than tracking coronitirus.

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