Abstract: We report in vivo selection of a severe acute respiratory syndrome coronavirus 2 spike mutation (Q493R) conferring simultaneous resistance to bamlanivimab and etesivimab.
Introduction: Emergence of SARS-COV-2 spike protein escape mutation Q493R after treatment for COVID-19.
Introduction: However, the May 3 specimen showed a secondary A1478G peak in the spike protein gene, corresponding to the spike Q493R mutation, which became predominant by May 8 (Ct 18; GenBank accession no.
Introduction: In a flow cytometry competitive assay, Q493R reduces the 50% inhibitory concentration >100-fold for bamlanivimab and 4
An overview of the preclinical discovery and development of bamlanivimab for the treatment of novel coronavirus infection (COVID-19): reasons for limited clinical use and lessons for the future.
PMID: 34304682
2021
Expert opinion on drug discovery
Conclusion: The strategy of antibody cocktails could represent a temporary solution (cocktails cannot escape resistance for long time if occurrence of variants is too frequent), although their economic sustainability should be carefully considered: resistance to the bamlanivimab-etesevimab cocktail due to Q493R mutation has indeed already been reported, although fitness of such strain remains unconfirmed.
SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2.
Conclusion: While mutations Q493R, R408I, Q493H, P384S, and N501T can also be disruptive, but mutations N439K, V367F, and S477R are not as disruptive as other rapidly growing ones.
Table: Q493R
Mutations in the SARS-CoV-2 spike protein modulate the virus affinity to the human ACE2 receptor, an in silico analysis.
Abstract: On the other hand, several mutants, including the most prevalent N501Y and B.1.1.7 variants, as well as the K444R, L455F, Q493R, and Y505W variants exhibited lower binding free energy as compared to the WT spike.
Result: The other investigated mutants, including the B.1.1.7 (-13.4 kcal/mol), K444R (-13.8 kcal/mol), L455F (-13.7 kcal/mol), Q493R (-13.5 kcal/mol) and Y505W (-14.4 kcal/mol) had the binding free energy lower than the WT spike protein, which indicated their higher affinity for the human ACE2 receptor.
Result: The substitutions G476A,
Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016.
Result: However, there are some sites where single mutations escape binding by both LY-CoV555 and LY-CoV016, and as a result a 1:1 cocktail of the 2 antibodies is escaped by several single mutations, including I472D, G485P, and Q493R/K (Figures 1A and S2; see the magnifiable interactive maps at https://jbloomlab.github.io/SARS-CoV-2-RBD_MAP_LY-CoV555/ to examine these mutations at higher resolution).
Result: We also note that single mutations that escape both antibodies (Q493R and Q493K) have been observed in a handful of sequenced isolates (Figure 2A).
Figure: Mutations with notable frequencies are labeled, and those discussed in the text are colored to key with (B) or to highlight observed cocktail escape mutations (Q493K/R).
Pan-India novel coronavirus SARS-CoV-2 genomics and global diversity analysis in spike protein.
Result: Of note, a Q493R mutation, which may impact ACE-2 affinity, was observed in the S gene at day 23.
Case Report: Paucisymptomatic College-Age Population as a Reservoir for Potentially Neutralization-Resistant Severe Acute Respiratory Syndrome Coronavirus 2 Variants.
PMID: 34544043
2021
The American journal of tropical medicine and hygiene
Conclusion: BV-1 is genetically distinct from previously reported B.1.1.7/Q493R variants, forming a new cluster along with 45 other non-Q493R B.1.1.7 sequences, collected January 25 to March 11 from the same on-campus population.
Conclusion: Based on this, it is inferred that the Q493R mutation of BV-1 may confer resistance to some neutralizing antibodies, though we have not directly tested the neutralizing activity.
Conclusion: It was recently reported that there are four major epitope classes on the SARS-CoV-2 spike protein receptor-binding domain where neutralizing antibodies bind, and that Q493R (BV-1) and E484K (not found in BV-1, but important in B.1.351 and B.1.617 variants) mediate roughly equivalent levels of resistance to only class-2 neutralizing antibodies, as def