BREAKING🔔 The 14th preprint from G2P-Japan🇯🇵 is out @biorxivpreprint. We illuminated the evolutionary rule underlying the convergent evolution of #Omicron and the virological characteristics of one of the latest lineages of concern, BQ.1.1. Please RT. 1/
biorxiv.org/content/10.110…
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 shining young talents, @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 increasing relative basic reproduction number (Re) (left), and BQ.1.1, which harbors all five convergent substitutions, showed the highest fitness among the viruses investigated (right). 5/
Neutralization assay showed that BQ.1.1 is more resistant to breakthrough BA.2/5 infection sera than BA.5. 6/
We have shown lines of data suggesting the close association of viral fusogenicity and intrinsic pathogenicity. For instance, both BA.5 (the link is shown below⬇️) and BA.2.75, descendants of BA.2, are more fusogenic and pathogenic than parental 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

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More from @SystemsVirology

Dec 5
#拡散希望 速報🔔 G2P-Japan🇯🇵のプレプリント第14弾「オミクロン亜株の収斂進化とBQ.1.1の性状解析」をbioRxiv @biorxivpreprint に発表しました。本研究では、オミクロン亜株の進化を描出し、 #オミクロン BQ.1.1(通称 #ケルベロス)の特徴を解明しました。以下まとめ⬇️ 1/
biorxiv.org/content/10.110…
2022年半ばのBA.5株の出現以降、世界を席巻する新しい変異株の出現が見られず、これまでのような「全とっかえ」の置き換わりが進んでいません。また逆に、世界中で多様化した #オミクロン亜株#収斂進化 していることが指摘されています。2/
2022年末現在、その最先端に位置するのが、5つのスパイクの収斂進化サイトの変異(#R346T #K444T #L452R #N460K #F486V)をコンプリートした、BQ.1.1株です。添付の系統樹が示すように、BQ.1.1はBA.5の子供にあたる株です。3/
Read 10 tweets
Dec 5
BREAKING🔔 The 15th paper from G2P-Japan🇯🇵 is out at iScience @iScience_CP. We revealed that the virological features of #Omicron BA.1 variant are determined by the spike #S375F mutation. Please RT. 1/6
cell.com/iscience/fullt…
We have demonstrated that the Omicron BA.1 spike exhibits 1) decreased efficiency of spike cleavage and 2) attenuated fusogenicity:
Cf. The 5th paper from G2P-Japan🇯🇵↓
nature.com/articles/s4158…
However, it remained unclear which mutation(s) determine these BA.1’s features. 2/6
1️⃣Our comprehensive screening experiments revealed that these BA.1's features are determined by its receptor binding domain and particularly, only #S375F mutation is responsible. 3/6
Read 7 tweets
Dec 5
#拡散希望 G2P-Japan🇯🇵の論文第15弾「#S375F:オミクロンBA.1を特徴づける変異」を、iScience @iScience_CP に発表しました。初代オミクロン である #BA1 の特徴が、#S375F というスパイクのたったひとつの変異で規定されることを解明しました。
以下、本研究の概要です。1/6
cell.com/iscience/fullt…
#オミクロン BA.1株は、①スパイクタンパク質の開裂効率の低下と、②低い膜融合活性、というふたつの特徴を持つことが明らかになっています。

参考:G2P-Japan🇯🇵論文第5弾↓
nature.com/articles/s4158…

しかし、スパイクタンパク質のどの変異がこれらの特徴を決めているのかは不明でした。2/6
1️⃣本研究ではまず、大規模なスクリーニング実験の結果、BA.1株の上記のふたつの特徴は、スパイクタンパク質のreceptor binding domainに規定され、その中でも特に、#S375F というたったひとつの変異によって特徴づけられることを明らかにしました。3/6
Read 8 tweets
Oct 10
BREAKING🔔 The 14th paper from G2P-Japan🇯🇵 is out at Cell Host & Microbe @cellhostmicrobe. #Omicron BA.2.75 (aka #Centaurus) seems to be more contagious than BA.5 and more pathogenic than the original BA.2. Please RT. 1/16
cell.com/cell-host-micr…
BA.2.75, emerged in India🇮🇳, is classified as VOC-LUM (variant of concern linage under monitoring) by WHO on July 7. Here we elucidated the transmissibility, sensitivity to antiviral immunity & drugs, and intrinsic pathogenicity of BA.2.75. 2/16
who.int/activities/tra…
BA.2.75 is a descendant of BA.2. However, BA.2.75 is phylogenetically different from BA.5, the currently predominant BA.2 descendant. BA.2.75 spike bears nine substitutions, but only a substitution is shared with BA.5 spike. 3/16 Image
Read 16 tweets
Oct 10
#拡散希望 速報🔔 G2P-Japan🇯🇵の論文第14弾(カウントどこかでずれてました)を、Cell Host & Microbe @cellhostmicrobe に発表しました。本研究では、#オミクロン BA.2.75株(通称 #ケンタウロス)のウイルス学的性状を解明しました。
以下、本研究の概要です。1/18
cell.com/cell-host-micr…
2022年5月、インド🇮🇳で、スパイクタンパク質に新たな変異を獲得した #オミクロン 系統の亜株「BA.2.75」が確認されました。BA.5による第7波真っ只中の日本においても、BA.2.75の市中感染は各所で確認されています。2/18
これまでに見られなかった変異の出現や世界各国での検出を受けて、WHOは7月7日に、BA.2.75株を「懸念される変異株(VOC)における監視下の系統(VOC-LUM; variant of concern linages under monitoring)」に分類し、注視しています。3/18
who.int/activities/tra…
Read 18 tweets
Sep 14
BREAKING🔔 The 10th paper from G2P-Japan🇯🇵 is out at Cell @CellCellPress . #Omicron BA.5 variant is more contagious and pathogenic than BA.2 variant. Please RT. 1/8
cell.com/cell/fulltext/…
Recently, Omicron BA.2 subvariants that bear additional substitutions in the spike proteins emerged and started outcompeting original BA.2 - e.g., BA.2.12.1 (+L452Q/S704L) in US🇺🇸 and BA.4 & BA.5 (+L452R/HV69-70del/F486V/R493Q) in South Africa🇿🇦. 2/8
1⃣ Statistical analysis shows that the effective reproduction numbers of BA.2.12.1, BA.4 & BA.5 are ~1.2-fold higher than that of BA.2. 3/8
Read 9 tweets

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