Discussion: Although H014 and P2C-1F11 neutralized all of the 501Y.V2 variants we tested in the present study, we previously showed that some other mutations in the RBD region lead to decreased neutralizing capability for P2C-1F11 (A475V) and H014 (A435S and Y508H).
SARS-CoV-2 variants combining spike mutations and the absence of ORF8 may be more transmissible and require close monitoring.
PMID: 33676232
2021
Biochemical and biophysical research communications
Result: Eleven spike mutations were not found associated with ORF8 variants: L8V/W, N234Q, Q239K, L452R, A475V, G476S, V483A, F490L, V615I/F, A831V and D839Y/N/E.
Analysis of SARS-CoV-2 mutations in the United States suggests presence of four substrains and novel variants.
Result: Although mutatin A475V on the RBM has a negative binding free energy change with a relatively high frequency (5) on the RBM, the much higher frequencies of two mutations G476S (7) and V483A (31) with positive binding free energy change suggests that the mutations in Cluster C may strengthen the infectivity of SARS-CoV-2 in general.
Discussion: Notably, the presence of the A475V, L452R, V483A, and F490L mutations in the RBD domain of SARS-CoV-2 was shown to decrease the neutralizing activity of antibody and might impede the development of therapeutic antibodies (Li et al, 2020).
Comprehensive annotations of the mutational spectra of SARS-CoV-2 spike protein: a fast and accurate pipeline.
PMID: 32954666
2021
Transboundary and emerging diseases
Result: We also found aa substitutions at six positions within the RBD region that are directly involved in binding with ACE-2 receptor (Wang et al., 2020; Yuan et al., 2020) including N439K (Scotland, Romania), L455F (England), A475V (USA, Australia), and F456L, Q493L and N501Y (USA) (Data S2).
The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity.
Abstract: Most variants with amino acid change at receptor binding domain were less infectious, but variants including A475V, L452R, V483A, and F490L became resistant to some neutralizing antibodies.
Table: A475V
Discussion: A475V reduced the sensitivity to 6 mAb out of the 13 mAb used in this study, whereas F490L reduced the sensitivity to neutralization by 3 mAbs.
Discussion: Another RBD variant A475V sits in the binding epitope of RBD.
Discussion: Moreover, some variants, including N439K, L452R,
A SARS-CoV-2 vaccine candidate would likely match all currently circulating variants.
Result: To be noted, A475V on the RBM has a negative binding affinity change with a relatively high frequency compared to the other 3 mutations in Cluster C.