Difference between revisions of "Time Course"
m (→N460K) |
|||
| Line 2: | Line 2: | ||
<big>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:<br /></big> | <big>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:<br /></big> | ||
===N460K=== | ===N460K=== | ||
| − | <big>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 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 a new hydrogen bond with the electrostatically complementary ACE2 surface.<ref>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).</ref><ref>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).</ref><ref name=":0">Qu, P. ''et al.'' Evasion of neutralizing antibody responses by the SARS-CoV-2 BA.2.75 variant. ''Cell Host Microbe'' '''30,''' (2022).</ref> Moreover, this mutation | + | <big>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 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 a new hydrogen bond with the electrostatically complementary ACE2 surface.<ref>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).</ref><ref>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).</ref><ref name=":0">Qu, P. ''et al.'' Evasion of neutralizing antibody responses by the SARS-CoV-2 BA.2.75 variant. ''Cell Host Microbe'' '''30,''' (2022).</ref> Moreover, this mutation grants the virus with enhanced immune evasive capability and fusogenicity for better syncytia formation.<ref name=":0" /><br /></big> |
===R346T, R368I, and V445P=== | ===R346T, R368I, and V445P=== | ||
Revision as of 16:25, 30 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 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 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, R368I, 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.
F486V/S and K444T
F486V mutation previously showed up in BA.4&5 lineage. This mutation also shows up in the BQ.1 lineage and exhibits polymorphism in the XBB lineage, with the mutation from Phenylalanine to Serin (F486S). This mutation facilitates the escape from class I and II mAbs and the DMS study also reveals the same immune evasion capability over COV2-2832 mAb. deLemus outlines the mutation activity in this site by March 2022. The mutation K444T is reported in BQ.1 as well. This mutation has been reported to abolish the 2X324-neutralizing activity with various amino acids. deLemus also outlined the mutation in this site by the end of 2021.
- ↑ 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).