Thread by @SystemsVirology

BREAKING🔔 The 21st paper from G2P-Japan🇯🇵 is out at Nature Communications @NatureComms . We illuminated the virological characteristics of SARS-CoV-2 XBB variant (aka #Gryphon), generated by the recombination of two #Omicron subvariants. Please RT! 1/
nature.com/articles/s4146…

In late 2022, the Omicron subvariants have highly diversified. An example is BQ.1.1, which have convergently acquired amino acid substitutions at five critical residues in the spike protein: R346T, K444T, L452R, N460K & F486V. We reported it as below⬇️ 2/

https://twitter.com/systemsvirology/status/1656624444134281216

Another variant of concern is XBB. First, two young talents, @jampei2 & @SpyrosLytras, showed that XBB emerged by recombination of two co-circulating BA.2 lineages, BJ.1 & BM.1.1.1 (a progeny of BA.2.75), during summer 2022. 3/

We showed that the Re values of XBB lineages are comparable with or slightly higher than those of BQ.1 lineages, and notably, XBB and BQ.1 lineages are becoming dominants in Eastern and Western regions of the world, respectively. 4/

Neutralization assay revealed that XBB.1 is the most profoundly resistant variant to BA.2/5 breakthrough infection sera ever (!!). >30-fold more resistant to BA.2 breakthrough infection sera than BA.2, >13-fold more resistant to BA.5 breakthrough infection sera than BA.2... 5/

XBB.1 spike is more fusogenic than BA.2.75 spike. Notably, the recombination breakpoint is located in the receptor-binding domain of spike, and each region of recombined spike conferred both immune evasion and augmented fusogenicity to the XBB.1 spike. 6/

Finally, the intrinsic pathogenicity of XBB.1 in hamsters is comparable to or even lower than that of BA.2.75. 7/

Our multiscale investigation provided evidence suggesting that #XBB is the first documented example of a SARS-CoV-2 variant that increased its fitness (Re) through recombination rather than substitutions. 8/8