A structural dynamic explanation for observed escape of SARS-CoV-2 BA.2 variant mutation S371L/F
Miller, N. L.; Clark, T.; Raman, R.; Sasisekharan, R.
Show abstract
The SARS-CoV-2 Omicron sub-variants BA.1 and BA.2 have become the dominant variants worldwide due to enhanced transmissibility and immune evasion. In response to the rise of BA.1 and BA.2, two recent studies by Liu et al. and Iketani et al. provide a detailed analysis of loss of therapeutic antibody potency through evaluation of escape by pseudotyped viruses harboring BA.1 and BA.2 receptor binding domain (RBD) point mutations. Surprisingly, Liu et al. and Iketani et al. observed a profoundly broad escape effect for the individual mutations S371L and S371F. This result cannot be explained by known escape mechanisms of the SARS-CoV-2 RBD, and conflicts with existing computational and experimental escape measurements for S371 mutations performed on monomeric RBD. Through an examination of these conflicting datasets and a structural analysis of the antibodies assayed by Liu et al. and Iketani et al., we propose a mechanism to explain S371L/F escape according to a perturbation of spike trimer conformational dynamics that has not yet been described for any SARS-CoV-2 escape mutation. The proposed mechanism is relevant to Omicron and future variant surveillance as well as therapeutic antibody design.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Broadly neutralizing antibodies targeting a conserved silent face of spike RBD resist extreme SARS-CoV-2 antigenic drift 96%
- Mapping essential somatic hypermutations in a CD4-binding site bNAb informs HIV-1 vaccine design 95%
- Epistasis in the receptor binding domain of contemporary H3N2 viruses that reverted to bind sialylated diLacNAc repeats 95%
Similar papers in this journal
- Neutralizing antibodies induced in immunized macaques recognize the CD4-binding site on an occluded-open HIV-1 envelope trimer 96%
- Structural and Biochemical Rationale for Enhanced Spike Protein Fitness in Delta and Kappa SARS-CoV-2 Variants 95%
- Sequence signatures of two IGHV3-53/3-66 public clonotypes to SARS-CoV-2 receptor binding domain 94%
Similar papers in this journal
- Bispecific antibodies combine breadth, potency, and avidity of parental antibodies to neutralize sarbecoviruses 94%
- Recognition determinants of improved HIV-1 neutralization by a heavy chain matured pediatric antibody 94%
- Broad SARS-CoV-2 Neutralization by Monoclonal and Bispecific Antibodies Derived from a Gamma-infected Individual 94%
Similar papers in this journal
- Structural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody 95%
- Deep Mining of the Human Antibody Repertoire Identifies Frequent and Immunogenetically Diverse CDRH3 Topologies Targetable by Vaccination 93%
- Structural insights into VRC01-class bnAb precursors with diverse light chains elicited in the IAVI G001 human vaccine trial 93%
Similar papers in this journal
- HIV-1-envelope trimer transitions from prefusion-closed to CD4-bound-open conformations through an occluded-intermediate state 93%
- Landscape of infection enhancing antibodies in COVID-19 and healthy donors 92%
- The Impact of Gag Non-Cleavage Site Mutations on HIV-1 Viral Fitness from Integrative Modelling and Simulations 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.