Inhibitor screening using microarray identifies the high capacity of neutralizing antibodies to Spike variants in SARS-CoV-2 infection and vaccination.
Result: Using a 2-fold minimum as the selection criteria, 10 mutations that weaken the S-ACE2 interaction were identified, including A372T, F377L, G446V, F456E
Result: Using statistical analysis, the neutralization of convalescent serum NAbs to eight mutated proteins was significantly decreased, including 4 known escape mutations [K417N, G446V, F490L, K417N/E484K/N501Y (B.1.351 strain)] and 4 newly identified escape mutations (A372S, F456E, N487R, Y505C) (Figure 4F-G).
Allosteric Determinants of the SARS-CoV-2 Spike Protein Binding with Nanobodies: Examining Mechanisms of Mutational Escape and Sensitivity of the Omicron Variant.
PMID: 35216287
2022
International journal of molecular sciences
Introduction: These studies identified a group of common resistant mutations in the dynamic RBM region (F490S, E484K, Q493K/R, F490L, F486S, F486L, and Y508H) that evade many individual nanobodies.
Result: The mutational sensitivity map also sheds some light on the structure-functional role of sites targeted by common resistant mutations (F490S, E484K, Q493K/R, F490L, F486S, F486L, and Y508H) that evade many individual nanobodies.
A comprehensive overview of identified mutations in SARS CoV-2 spike glycoprotein among Iranian patients.
Introduction: While most of alterations in the receptor binding domain (RBD) reduce infectivity, A475V, L452R, V483A, and F490L variants induce resistance to some neutralizing antibodies.
Reduced sensitivity of the SARS-CoV-2 Lambda variant to monoclonal antibodies and neutralizing antibodies induced by infection and vaccination.
Introduction: Meanwhile, the F490L mutation is resistant to some neutralizing antibodies, and the F490S mutation may affect the efficiency of existing vaccines.
Discussion: Our previous study found that the L452R and F490L mutations can cause escape from mAb X593, consistent with the results of the L452Q and F490S mutations in the present study.
Discussion: Our previous study showed that both F490 and L452 are located at the binding site of mAb 9G11 to the RBD, and experimentally verified that F490L and L452R mutations can cause escape from mAb 9G11, which is consistent with the results presented here.
Discussion: Taken together, our results suggest that the
Myxobacterial depsipeptide chondramides interrupt SARS-CoV-2 entry by targeting its broad, cell tropic spike protein.
PMID: 34463219
2021
Journal of biomolecular structure & dynamics
Introduction: The top-binding ligands were additionally screened against biologically significant SARS-CoV-2 mutations occurring in the RBD of the S protein such as N501Y, E484K, K417N/T, A475V, I472V, L452R, V483A, F490L, S477N and N439K along with the United Kingdom, South African and Brazilian SARS-CoV-2 variants.
Result: Li and co-workers identified single amino acid substitutions in the viral spike RBD (A475V, I472V
Characterization of SARS-CoV-2 worldwide transmission based on evolutionary dynamics and specific viral mutations in the spike protein.
PMID: 34419160
2021
Infectious diseases of poverty
Table: F490L
Review of the mechanisms of SARS-CoV-2 evolution and transmission.
Introduction: Many of these co-mutation sets involve vaccine-escape mutations predicted in our early work: S494P, Q493L, K417N, F490S, F486L, R403K, E484K, L452R, K417T, F490L, E484Q, and A47
Introduction: We noted that L452R, V483F/A, E484K/Q, F486L, F490L/S, Q493K/R, and S494P could disrupt Eli Lilly mAbs.
A Combination of Receptor-Binding Domain and N-Terminal Domain Neutralizing Antibodies Limits the Generation of SARS-CoV-2 Spike Neutralization-Escape Mutants.
Result: As it could be anticipated from the relevant CAS data discussed above, the in silico mutagenesis results for these further four viral protein residues into the reported variants (Y449D/F/H/N/S, L452M/Q/R, T470A/I/K/N and F490L/S/V/Y) also confirm a remarkable degree of tolerability to substitution at each of these spike positions in binding the LY-CoV555 Ab, with the remarkable exceptions of the L452R and:albeit to a lower extent:the F490S mutations.
Result: led to the following list of naturally occurring mutations at the SARS-CoV-2 spike protein residues contacting the LY-CoV555 mAb: PMID: 34720581
2021
Bioinformatics and biology insights
Result: We also analyzed the effect of 27 missense variants of SARS-CoV-2 spike protein (RBD) on the binding interaction of spike protein with ACE2 and observed that L452Q, T478K, L455F, F456L, S459F, A475V, N439K, L452R, T470N, E484D, E484A, E484K, E484Q, F486L, S494P, S494L, N501T,