In late 2022, the SARS-CoV-2 omicron BQ.1 and XBB lineages, characterised by amino acid substitutions within the spike (S) protein that enhance viral health, had turn into predominant within the western (BQ.1) and japanese (XBB) hemispheres.
1
- Ito J
- Suzuki R
- Uriu Ok
- et al.
Convergent evolution of the SARS-CoV-2 Omicron subvariants resulting in the emergence of BQ.1·1 variant.
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- Tamura T
- Ito J
- Uriu Ok
- et al.
Virological traits of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants.
The BQ.1 lineages are descendants of BA.5, whereas the XBB lineage is the recombinant of two extremely diversified BA.2 lineages.
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- Tamura T
- Ito J
- Uriu Ok
- et al.
Virological traits of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants.
In 2022, we elucidated the traits of a wide range of newly rising SARS-CoV-2 omicron subvariants.
1
- Ito J
- Suzuki R
- Uriu Ok
- et al.
Convergent evolution of the SARS-CoV-2 Omicron subvariants resulting in the emergence of BQ.1·1 variant.
,
2
- Tamura T
- Ito J
- Uriu Ok
- et al.
Virological traits of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants.
,
3
- Yamasoba D
- Kimura I
- Nasser H
- et al.
Virological traits of the SARS-CoV-2 Omicron BA.2 spike.
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4
- Yamasoba D
- Kosugi Y
- Kimura I
- et al.
Neutralisation sensitivity of SARS-CoV-2 omicron subvariants to therapeutic monoclonal antibodies.
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5
- Kimura I
- Yamasoba D
- Tamura T
- et al.
Virological traits of the SARS-CoV-2 Omicron BA.2 subvariants, together with BA.4 and BA.5.
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6
- Saito A
- Tamura T
- Zahradnik J
- et al.
Virological traits of the SARS-CoV-2 Omicron BA.2.75 variant.
On the finish of 2022, the XBB.1.5 variant, a descendant of XBB.1 that acquired the S:S486P substitution, emerged and is quickly spreading within the USA (appendix pp 6–7), and is the newest variant of concern.
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WHO
XBB.1.5 speedy threat evaluation.
Though the options of XBB.1.5 have been reported by Yue and colleagues,
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- Yue C
- Track W
- Wang L
- et al.
Enhanced transmissibility of XBB.1.5 is contributed by each robust ACE2 binding and antibody evasion.
a complete understanding of the virological traits of newly rising variants is required for sustained world well being. Our epidemic dynamics evaluation (appendix pp 6–7) revealed that the relative efficient replica quantity (Re) of XBB.1.5 is 1·2 instances larger than that of the parental XBB.1, and XBB.1.5 is outcompeting BQ.1.1, the predominant lineage within the USA as of December, 2022 (appendix pp 6–7). Our information counsel that XBB.1.5 will quickly unfold worldwide within the close to future (appendix pp 6–7).
We subsequent investigated the virological options of XBB.1.5. Yeast floor show assay confirmed that the dissociation fixed worth of XBB.1.5 S receptor-binding area from the human ACE2 receptor is considerably (4·3 instances) decrease than that of XBB.1 S receptor-binding area (
appendix pp 6–7). Experiments utilizing lentivirus-based pseudoviruses additionally confirmed roughly 3-fold elevated infectivity of XBB.1·5 in contrast with XBB.1 (
appendix pp 6–7). These outcomes counsel that XBB.1.5 reveals a remarkably robust affinity to the human ACE2 receptor, which is attributed to the S486P substitution. Furthermore, neutralisation assay revealed that XBB.1.5 was robustly proof against BA.2 breakthrough an infection sera (41-fold versus B.1·1, 20-fold versus BA.2) and BA.5 breakthrough an infection sera (32-fold versus B.1·1, 9·5-fold versus BA.5;
appendix pp 6–7).
Throughout investigations, we noticed {that a} subset of the XBB.1.5 variant reverted the deletion of 144Y in S (S:Y144del;
appendix pp 6–7). As we beforehand confirmed that the S:Y144del mutation confers an elevated immune escape functionality,
2
- Tamura T
- Ito J
- Uriu Ok
- et al.
Virological traits of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants.
we hypothesised that the reversion of S:Y144del (ins144Y) impacts the virological options of XBB.1.5. Nonetheless, XBB.1.5 with out S:Y144del (XBB.1.5 + ins144Y) exhibited a decrease Re in contrast with the unique XBB.1.5 (appendix pp 6–7). Lentivirus-based pseudovirus assays confirmed that the 144Y insertion elevated the infectivity of XBB.1 however didn’t have an effect on the infectivity of XBB.1.5 (appendix pp 6–7). Moreover, neutralisation assays confirmed that the 144Y insertion considerably elevated the sensitivity to BA.2 and BA.5 breakthrough an infection sera (appendix pp 6–7). Altogether, our information counsel that the reversion of S:Y144del doesn’t enhance the viral properties of XBB.1.5, together with health.
In abstract, our outcomes counsel that XBB.1.5 is probably the most profitable XBB lineage as of January, 2023, because it has acquired the S:S486P substitution, which boosts its binding affinity to the ACE2 receptor with out compromising its exceptional immune resistance. Our information counsel that these virological options lead to larger transmissibility.
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