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Impact of new variants on SARS-CoV-2 infectivity and neutralization: A molecular assessment of the alterations in the spike-host protein interactions. | LitMetric

AI Article Synopsis

  • * It identifies specific mutations in the Delta variant that increase its ability to bind to ACE2 and evade certain antibodies, while still being susceptible to others like nanobody Nb20.
  • * The research emphasizes the need for detailed structural analysis to better predict how new SARS-CoV-2 variants could respond to existing treatments and immune defenses.

Article Abstract

The emergence of SARS-CoV-2 variants necessitates rational assessment of their impact on the recognition and neutralization of the virus by the host cell. We present a comparative analysis of the interactions of Alpha, Beta, Gamma, and Delta variants with cognate molecules (ACE2 and/or furin), neutralizing nanobodies (Nbs), and monoclonal antibodies (mAbs) using methods, in addition to Nb-binding assays. Our study elucidates the molecular origin of the ability of Beta and Delta variants to evade selected antibodies, such as REGN10933, LY-CoV555, B38, C105, or H11-H4, while being insensitive to others including REGN10987. Experiments confirm that nanobody Nb20 retains neutralizing activity against the Delta variant. The substitutions T478K and L452R in the Delta variant enhance associations with ACE2, whereas P681R promotes recognition by proteases, thus facilitating viral entry. The Ab-specific responses of variants highlight how full-atomic structure and dynamics analyses are required for assessing the response to newly emerging variants.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851820PMC
http://dx.doi.org/10.1016/j.isci.2022.103939DOI Listing

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