Updating results regarding convergent variants BU.1, BR.2, BM.1.1.1, CA.1, and XBB.
XBB is currently the most antibody-evasive strain tested, and BR.2, BM.1.1.1, CA.1 are more immune evasive than BA.2.75.2 and BQ.1.1.
biorxiv.org/content/10.110…
Similar to BQ.1.1, XBB also escapes Evusheld and Bebtelovimab. BU.1, BR.2, BM.1.1.1, CA.1, and XBB all displayed sufficient hACE2 binding capability.
XBB is significantly more immune evasive than BA.2.75.2 and BQ.1.1 against plasma from all breakthrough infections, comparable to or even exceeding SARS-CoV-1 level escaping capability. BR.2, BM.1.1.1 and CA.1 also exhibit very strong immune evasion, but less compared to XBB.
XBB's superior antibody escaping capability not only comes from the convergent RBD mutations, it's NTD mutations, V83A and 144-deletion, are also extremely good at escaping NTD-targeting neutralizing antibodies.
I believe there is still room for XBB to gain more mutations, such as L452R or K356T or both. BQ.1.1 may also evolve mutations on the NTD, such as the 144-del carried by BU.1, to catch up on immune evasion capability.
We will keep on updating results on these emerging convergent variants, if there is more. All data will be merged into the BioRxiv preprint we previously posted.
biorxiv.org/content/10.110…

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More from @yunlong_cao

Sep 23
Updating information regarding convergent variants BA.2.3.20, BN.1, BA.2.10.4, BN.2.1, BA.4.6.1, BQ.1, BQ.1.1.
In short, BA.2.75.2 and BQ.1.1 are the most antibody-evasive convergent variants tested, far exceeding BA.5 and approaching SARS-CoV-1 level. (1/4)
BA.2.75.2 is slightly more evasive than BQ.1.1 against plasma from BA.2/BA.5 breakthrough infections. Its due to the enriched NTD-NAbs elicited by BA.2/BA.5 infections, which BQ.1.1 can't escape. Note that these varaints are approaching SARS-CoV-1 level escaping capability. (2/4) Image
As expected, BQ.1.1 escapes Evusheld and bebtelovimab, making all clinically available antibody drugs ineffective. BQ.1.1 and BA.2.75.2 both displayed sufficient hACE2 binding capability. (3/4) Image
Read 4 tweets
Sep 16
Sharing our investigation on the unprecedented convergent RBD evolution of BA.2.75 and BA.5 on sites including 346, 356, 444-446, 450, 460, 486, which have generated highly concerning variants such as BA.2.75.2, BR.1, BJ.1, and BQ.1.1. (1/n)
biorxiv.org/content/10.110…
In this paper, we tried to solve the following three questions:
1) How immune evasive could these variants be?
2) Why do they evolve mutations on these converging sites?
3) What could this convergence evolution finally lead to? (2/n)
biorxiv.org/content/10.110…
As many have noticed, recent evolution of Omicron has led to numerous subvariants that exhibit high growth advantages over BA.5. Interestingly, mutations on their receptor-binding domain (RBD) converge on several hotspots, including R346, R356, K444, L452, N460 and F486. (3/n)
Read 21 tweets
Aug 10
Sharing some updates on our BA.2.75 study.
In brief, BA.2.75 shows high-level neutralization resistance to BA.5 breakthrough-infection plasma, due to the distinct RBD and NTD antigenicity exhibited by BA.2.75 and BA.4/BA.5. (1/n)
biorxiv.org/content/10.110…
~25 days after our previous report on BA.2.75, its growth advantage over BA.5 in India has become clearer. The question is whether this local spread would translate into a global prevail after the BA.4/BA.5 wave. (2/n) Image
One advantage of BA.2.75 is its extremely high hACE2 binding affinity. By solving the hACE2/Spike complex structure of BA.2.75, we showed that indeed R493Q reversion is the major contributor, independent of N460K. (3/n) Image
Read 11 tweets

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