Thread by @SystemsVirology

BREAKING🔔 The 20th paper from G2P-Japan🇯🇵 is out at Nature Communications @NatureComms. We illuminated the convergent evolution of #Omicron and characteristics of BQ.1.1 (aka #Cerberos). Please RT

20 papers in 28 months since the launch of G2P-Japan🎉 1/
nature.com/articles/s4146…

In late 2022, the Omicron subvariants have highly diversified. However, some lineages have convergently acquired amino acid substitutions at five critical residues in the spike protein: R346, K444, L452, N460 and F486. 2/

Omicron BQ.1.1 (aka #Cerberus), a descendant of BA.5, bears all five substitutions at the convergent sites: R346T, K444T, L452R, N460K, F486V. 3/

Here, we, particularly two young shining stars, @jampei2 & @SpyrosLytras, performed phylogenetic and epidemic dynamics analyses and showed that Omicron subvariants independently increased their viral fitness by acquiring the convergent substitutions. 4/

All five convergent substitutions (R346T, K444T, L452R, N460K & F486V) contributed to increase relative effective reproduction number (Re), and BQ.1.1, which harbors all five convergent substitutions, showed the highest fitness among the viruses investigated. 5/

Neutralization assay showed that BQ.1.1 is more resistant to breakthrough BA.2 and BA.5 infection sera than BA.5. 6/

We showed lines of data suggesting the close association of viral fusogenicity and intrinsic pathogenicity. For instance, both BA.5 and BA.2.75, descendants of BA.2, are more fusogenic and pathogenic than BA.2. 7/

Notably, the BQ.1.1 spike exhibited greater fusogenicity than the BA.5 spike, suggesting that BQ.1.1 is more pathogenic than BA.5. 8/

However, unexpectedly, experiments using hamsters showed that the pathogenicity of BQ.1.1 in hamsters is comparable to or even lower than that of BA.5.

Our multiscale investigations provide insights into the evolutionary trajectory of Omicron subvariants. 9/9