Immune-evading variants can emerge in SARS-CoV-2, researchers warn

immune evading variants can emerge in sars cov 2 researchers warn

Sumary of Immune-evading variants can emerge in SARS-CoV-2, researchers warn:

  • An international team of researchers has shown that a mutation within severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent responsible for the coronavirus disease 2019 (COVID-19) – enables the pathogen to evade antibody-mediated immunity while maintaining replication fitness and increasing viral loads..
  • The researchers showed that a variant in the viral spike protein called N439K enhanced binding affinity to the human host cell receptor angiotensin-converting enzyme 2 (ACE2) and resulted in immune escape from a panel of neutralizing monoclonal antibodies (mAbs) and from the polyclonal sera of recovered individuals..
  • “Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S [spike], highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics,”.
  • (C) Heatmap of Deep Mutational Scanning (DMS) hACE2 binding and expression data for RBM residues (Starr et al., 2020)..
  • These data are key to monitoring the spread and evolution of the virus, particularly the evolution of the spike protein (or S-protein) – the protein the virus uses to interact with ACE2 and enable the delivery of the viral genome into host cells..
  • The spike protein is the viral structure that is targeted by neutralizing antibodies following infection or vaccination and by the mAbs that are being tested in clinical trials..
  • Studies have shown that the spike variant D614G, which is now dominant across most of the globe, may have greater infectivity, while maintaining efficient spread and virulence, say Snell and team..
  • However, amino acid 614 lies outside of the spike receptor-binding domain (RBD) – the region targeted by most of the neutralizing antibody activity that occurs in the serum of people who have survived infection..
  • “Initial studies suggest that D614G actually exhibits increased sensitivity to neutralizing antibodies, likely due to its effects on the molecular dynamics of the spike protein,”.
  • Spike receptor binding motif (RBM) is main target of neutralizing antibodies Now, Snell and colleagues have examined the SARS-CoV-2 receptor binding motif (RBM), the primary target of neutralizing antibodies within the spike RBD..
  • The team showed that the RBM is the most divergent region of spike and less conserved than the RBD or the entire protein..
  • To understand how this structural plasticity might influence immune evasion, the researchers investigated the clinical and epidemiological impact, molecular features, and immune response to an RBM variant called N439K…

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