Abstract: We unveil, for the first time, that high-frequency mutations R346K/S, N439K, G446V, L455F, V483F/A, F486L, F490L/S, Q493L, and S494P might compromise some of mAbs in clinical trials.
Simultaneous evaluation of antibodies that inhibit SARS-CoV-2 variants via multiplex assay.
Result: COVA2-15 and C135 demonstrated escape to G446V, while COVA2-15 demonstrated a loss of binding and inhibition to S494P.
Discussion: It is interesting to note, however, that unlike higher affinity N501Y and S477N variants, F490L and G446V demonstrated the weakest EC50 values in our ACE2 binding assay (Figure 3D), but were observed at relatively high frequencies (Figure 3B), supporting the hypothesis that modestly deleterious mutations may have the potential to rise in prevalence if they confer escape from selective pressures, such as the immune response.
Discussion: We also found variant G446V, which has demonstrated resistance to REGEN10987 and C135, to be poorly neutralized by our panel of mAbs.
Insilico study on the effect of SARS-CoV-2 RBD hotspot mutants' interaction with ACE2 to understand the binding affinity and stability.
Result: Additionally, the mutation G446D compared to G446S and G446V shows a noteworthy effect on the binding affinity between RBD and ACE2.
Result: The variants with more negative binding free energy (high binding affinity) than the WT complex are N501Y, N501T, K417R, N501I, L455F, A475V, N501S, Y453F, Q493H, G446S, G446V, Q493L and Y495F
Table: G446V
A Comprehensive Molecular Epidemiological Analysis of SARS-CoV-2 Infection in Cyprus from April 2020 to January 2021: Evidence of a Highly Polyphyletic and Evolving Epidemic.
Result: In lineage B.1.1.29, F338X, F342X, A344P, V367L, G446V, P507L and V510L were each represented in a different sequence, and in lineage B.1.177, only the S477G mutation was found in the RBD in only one sequence.
Discussion: Namely, the uncommon G446V mutation has been reported to reduce serum binding and neutralization.
Epitope Classification and RBD Binding Properties of Neutralizing Antibodies Against SARS-CoV-2 Variants of Concern.
Result: A second group of RBD variants, L452R (15%), G446V (10%), and N440Y (5%) disrupted fewer NAb interactions, while all NAbs bound efficiently (>50%, relative to WT reference) to RBD variants T345I, A475V, and Y505W.
Result: Additional conserved RBD contacts within the C2 NAb epitope suggests RBD variants G446V, L452R, and S494P can also impact C2 interactions.
Result: Based on the in silico NAb epitope analysis, nine RBD variants that localize to the C1 ( PMID: 34004284
2021
Genomics
Table: G446V
Mutations in the SARS-CoV-2 spike protein modulate the virus affinity to the human ACE2 receptor, an in silico analysis.
Result: In our analysis the highest Miyata values, indicating the largest differences between the WT and spike protein mutants were found for the following residue substitutions: N501Y, F490S, Q493L, G446V, and Y508H.
Revealing the threat of emerging SARS-CoV-2 mutations to antibody therapies.
Abstract: We unveil, for the first time, that high-frequency mutations R346K/S, N439K, G446V, L455F, V483F/A, E484Q/V/A/G/D, F486L, F490L/V/S, Q493L, and S494P/L might compromise some of mAbs in clinical trials.
Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization.
Result: G446D was resistant to SARS2-2, SARS2-32, and SARS2-38, but G446V acquired res
Result: Several mutants required higher (3-5-fold) concentrations of hACE2 to block infection, including substitutions at T345A, T345N, G446D, G446V, E484D, and F486Y.
Result: The penetrance of the remaining substitutions among clinical isolates is relatively low, with G446V, T478I, E484K, S477I, and S494P ranking 79, 102, 123, 135, and 146 of the top 150 variants in S or roughly 0.05% of sequenced variants.
SARS_CoV_2 mutation literature information.
PMID: 
2021
Infectious diseases of poverty
Browser Board
Co-occurred Entities
Filtrator
ViMRT