ArticleMicrobiology spectrum2026
Antibody-mediated SARS-CoV-2 entry and conformational regulation.
Article in Microbiology spectrum, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Antibody-mediated entry (AME) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into monocytes and macrophages has been linked to activation of inflammatory phenotypes that are associated with severe coronavirus disease 2019 (COVID-19), but why only some antibodies mediate this entry while others do not is unknown. However, it has been demonstrated that conformational dynamics of the SARS-CoV-2 receptor-binding domain (RBD) are critical to viral entry, and that antibodies targeting the RBD can conformationally regulate these dynamics. Here, we identified four groups of RBD-specific monoclonal antibodies (mAbs) that target unique epitopes on the SARS-CoV-2 RBD and are also associated with different RBD conformational regulation and AME abilities. Steric clash quantification elucidated a structural basis for differences in conformational regulation by these antibody groups. We found that some, but not all, antibody groups were able to mediate entry into THP1-derived macrophages, and also found that this entry was inhibitable by antibodies in other groups. Collectively, these results suggest that there is a connection between RBD conformational regulation, epitope, and AME for antibodies targeting SARS-CoV-2. This connection improves understanding of the AME mechanism and how to inhibit AME for SARS-CoV-2, which has potential applications in the continued development of safe and effective vaccines and therapeutics for COVID-19 and related diseases.IMPORTANCEAntibody-mediated entry (AME) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into immune cells and resulting activation of inflammatory pathways is increasingly being associated with coronavirus disease 2019 (COVID-19) disease severity. Vaccination against COVID-19 remains one of our strongest tools to prevent these effects; vaccines continue to protect patients from both severe and long COVID-19 symptoms, and serum from vaccinated individuals was shown not to cause AME in immune cells
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