Result: In contrast to the invariant residues, 9 ACE2 binding residues (K417, G446, L455, A475, G476, E484, F486, and N501) have undergone significant sequence variation ( Figure 2 ) with the largest frequencies occurring at four positions: N501Y (0.208%), E484K (0.079%), Y453F (0.062%), and F486L (0.059%).
Result: The N501Y variant, which occurs at the highest frequency, is the only residue located within the RBD knob, while Y453F is located in the RBD base and E484K and F486L are localized in the tip ( Figure 2A ).
Result: Thus, C1 NAb epitopes are predicted to be sensitive to K417N/T,
Bioinformatics Analysis Unveils Certain Mutations Implicated in Spike Structure Damage and Ligand-Binding Site of Severe Acute Respiratory Syndrome Coronavirus 2.
PMID: 34121839
2021
Bioinformatics and biology insights
Result: Although F486L and N501T is not predicted that does not damage the structure of the spike protein (Table 2), it has been stated that the N501T and F486L mutations affect the stability of the spike protein.
Table: F486L
SARS-CoV2 spike protein gene variants with N501T and G142D mutation-dominated infections in mink in the United States.
PMID: 34109885
2021
Journal of veterinary diagnostic investigation
Abstract: (173,277) SARS-CoV2 sequences deposited in GISAID from December 2019 to March 12, 2021, and identified 2 dominant novel variants, the N501T-G142D variant and N501T-G142D-F486L variant, in the U.S.
Abstract: The N501T mutation occurred 2 mo earlier in humans than in mink in the United States, and the novel N501T-G142D and N501T-G142D-F486L variants were found in humans prior to mink.
Introduction: Among 454 Danish mink SARS-CoV2 sequences, 3 had N501T mutations as described earlier, none had G142D or
Vaccine-escape and fast-growing mutations in the United Kingdom, the United States, Singapore, Spain, India, and other COVID-19-devastated countries.
Abstract: A list of most likely vaccine escape mutations is given, including S494P, Q493L, K417N, F490S, F486L, R403K, E484K, L452R, K417T, F490L, E484Q, and A475S.
Conclusion: We report that rapidly growing mutations S494P, Q493L, K417N, F486L, F490S, R403K, E484K, K417T,
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.
Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines.
Introduction: To assess the neutralization breadth of RBD-NP-elicited Abs, we evaluated serum neutralizing activity against a panel of pseudotyped viruses comprising wild-type (D614G) SARS-CoV-2 S and nine single-residue SARS-CoV-2 RBD mutants detected in clinical isolates (G446S, Y453F, L455F, T478I, E484A/K, F486L, S494P, and N501Y) as well as the B.1.1.7 (H69-V70 deletion, Y144 deletion, N501Y, A570D, P681H, T716I, PMID: 33568759
2021
Scientific reports
Conclusion: In the RBD region, S477G [CBCTT(S)CCCCC CBCTT(S)CCCEC], P479L [CTTSC(C)CCCCC CTTSC(C)CECCC], V483A [CCCCC(C)CTTTC CCCCC(C)CCTTC], and F486L [CCCCT(T)TCBCS CCCEC(T)TCBCS] are four mutations having protein structure change potential.
Conclusion: Of these, only three mutations are in the RBD region: V483A [eebbb(b)bebeb eebbb(b)bbbeb], G485R [bbbbb(e)bebee bbbbb(b)bebee], and F486L [bbbbe(b)ebeeb bbbbb(e)ebeeb].
Conclusion: Two mutations V483A and F486L are thus likely to make changes in both protein secondary structure and relative solvent accessibility in the PMID: 33384909
2020
PeerJ
Abstract: SARS-CoV-2 isolates from minks exhibited two amino acid substitutions (G261D, A262S) in the N-terminal domain of S protein and four (L452M, Y453F, F486L, N501T) in the receptor-binding motif (RBM).
Result: Fifteen unique mutations were identified in mink isolates (Table S2), four of which (L452M, Y453F, F486L, N501T) were located within the RBM of S protein.
Role of Long-range Allosteric Communication in Determining the Stability and Disassembly of SARS-COV-2 in Complex with ACE2.
Result: We also computed the relative binding strength (DeltaDeltaG) between the wild-type (WT) F486 SARS-CoV-2 and the mutant F486L.
Result: We tested the impact of this replacement by alchemically substituting N501 with a threonine, and we computed the relative binding free energy of ACE2 and RBD between the WT SARS-CoV-2 and the N501T mutant following the same thermodynamic cycle as for the F486L mutation.
Discussion: In addition, computational studies report a DeltaDeltaG for the F486A mutation that is somewhat larger than our result for the F486L substitution.
Discussion: Interestingly, the values for the DeltaDeltaG of F486L in SARS-CoV-2 and L472F in SARS-CoV are in excellent agreement.
SARS_CoV_2 mutation literature information.
PMID: 
2021
Immunity
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