Difference between revisions of "Time Course"
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===K444T and F486V/S=== | ===K444T and F486V/S=== | ||
| − | <big>Amino acid sites 444 and 486 have been exhibiting strong mutational | + | <big>Amino acid sites 444 and 486 have been exhibiting strong mutational signals since the end of 2021 and March 2022 respectively, based on our deLemus analysis. Mutation at the former site, K444T, is specific to the BQ.1 subvariant, which has been reported to hinder the binding of class III antibodies by abrogating its hydrogen bond and salt bridge formation with the spike glycoprotein.<ref name=":1">Qu, P. ''et al.'' Enhanced neutralization resistance of SARS-CoV-2 omicron subvariants BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2. ''Cell Host Microbe'' '''31,''' (2023).</ref> Residue at the latter location, on the other hand, has been identified to be polymorphic, as indicated by the fact that 2 major substitutions exist in this site, which are the F486V of the BA.4, BA.5, and BQ.1 strains, and F486S of the XBB recombinant subvariant. The crucial role of this phenylaniline residue as both an ACE2 and antibody binding site implicates that spike glycoproteins carrying the F486V/S mutations would possess enhanced immune evasion capabilities against certain class I and II antibodies at the cost of having lowered ACE2-binding affinities.<ref name=":1" /><ref>Tuekprakhon, A. ''et al.'' Antibody escape of SARS-CoV-2 omicron BA.4 and BA.5 from Vaccine and BA.1 Serum. ''Cell'' '''185,''' (2022).</ref><ref>Wang, Q. ''et al.'' Antibody evasion by SARS-CoV-2 omicron subvariants BA.2.12.1, BA.4 and BA.5. ''Nature'' '''608,''' 603–608 (2022).</ref></big> |
== References == | == References == | ||
Revision as of 01:06, 31 January 2023
Previously Confirmed Mutations
In the last 6 months, 3 new members of the omicron (B.1.1.529) lineage have emerged, and subsequently been recognized as variants of interest (VOI) by the World Health Organization (WHO), which are the BA.2.75, XBB, and BQ.1 subvariants that rose to prominence in July, August and October 2022 respectively. Each of these VOIs has brought along an array of novel mutable sites crucial for refining the viral fitness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Leading mutations identified by our deLemus analysis that emerged within the aforementioned timeframe are listed as follows:
N460K
Amino acid site 460, which corresponds to the N460K mutation, has been exhibiting a persistently strong mutational signal since February 2022, based on our deLemus analysis. Mutation at this site was first reported in the BA.2.75 strain, and was subsequently retained in the XBB and BQ.1 subvariants. The asparagine-to-lysine substitution introduces a cationic residue in the receptor binding motif (RBM) of the receptor binding domain (RBD), which increases the ACE2-binding affinity of the spike glycoprotein by enabling the formation of a new hydrogen bond with the electrostatically complementary ACE2 surface.[1][2][3] Moreover, this mutation grants the virus with enhanced immune evasive capability and fusogenicity for better syncytia formation.[3]
R346T, L368I, and V445P
These three mutations have never been reported in the previous variants and currently show up in the XBB variant. The mutation at site 346 was previously reported in the lambda variant, but with the amino acid Lysine(R346K) instead of Threonine(R346T) as in XBB. deLemus detected the mutation activity in this site by the end of 2021, which persistently exhibits high signal ever since. For site V445, deLemus also has detected the mutation signal in this site since April 2022. The DMS study reported an escape capability of this site over mAbs COV2-2449.
K444T and F486V/S
Amino acid sites 444 and 486 have been exhibiting strong mutational signals since the end of 2021 and March 2022 respectively, based on our deLemus analysis. Mutation at the former site, K444T, is specific to the BQ.1 subvariant, which has been reported to hinder the binding of class III antibodies by abrogating its hydrogen bond and salt bridge formation with the spike glycoprotein.[4] Residue at the latter location, on the other hand, has been identified to be polymorphic, as indicated by the fact that 2 major substitutions exist in this site, which are the F486V of the BA.4, BA.5, and BQ.1 strains, and F486S of the XBB recombinant subvariant. The crucial role of this phenylaniline residue as both an ACE2 and antibody binding site implicates that spike glycoproteins carrying the F486V/S mutations would possess enhanced immune evasion capabilities against certain class I and II antibodies at the cost of having lowered ACE2-binding affinities.[4][5][6]
References
- ↑ Zahradník, J. et al. SARS-CoV-2 variant prediction and antiviral drug design are enabled by RBD in vitro evolution. Nat Microbiol 6, 1188–1198 (2021).
- ↑ Makowski, E. K., Schardt, J. S., Smith, M. D. & Tessier, P. M. Mutational analysis of SARS-CoV-2 variants of concern reveals key tradeoffs between receptor affinity and antibody escape. PLOS Comput Biol 18, (2022).
- ↑ 3.0 3.1 Qu, P. et al. Evasion of neutralizing antibody responses by the SARS-CoV-2 BA.2.75 variant. Cell Host Microbe 30, (2022).
- ↑ 4.0 4.1 Qu, P. et al. Enhanced neutralization resistance of SARS-CoV-2 omicron subvariants BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2. Cell Host Microbe 31, (2023).
- ↑ Tuekprakhon, A. et al. Antibody escape of SARS-CoV-2 omicron BA.4 and BA.5 from Vaccine and BA.1 Serum. Cell 185, (2022).
- ↑ Wang, Q. et al. Antibody evasion by SARS-CoV-2 omicron subvariants BA.2.12.1, BA.4 and BA.5. Nature 608, 603–608 (2022).