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奥密克戎BA.2(B.1.1.529.2):成为下一个主导变体的可能性很大。

Omicron BA.2 (B.1.1.529.2): high potential to becoming the next dominating variant.

作者信息

Chen Jiahui, Wei Guo-Wei

机构信息

Department of Mathematics, Michigan State University, MI 48824, USA.

Department of Biochemistry and Molecular Biology, Michigan State University, MI 48824, USA.

出版信息

Res Sq. 2022 Feb 23:rs.3.rs-1362445. doi: 10.21203/rs.3.rs-1362445/v1.

Abstract

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly replaced the Delta variant as a dominating SARS-CoV-2 variant because of natural selection, which favors the variant with higher infectivity and stronger vaccine breakthrough ability. Omicron has three lineages or subvariants, BA.1 (B.1.1.529.1), BA.2 (B.1.1.529.2), and BA.3 (B.1.1.529.3). Among them, BA.1 is the currently prevailing subvariant. BA.2 shares 32 mutations with BA.1 but has 28 distinct ones. BA.3 shares most of its mutations with BA.1 and BA.2 except for one. BA.2 is found to be able to alarmingly reinfect patients originally infected by Omicron BA.1. An important question is whether BA.2 or BA.3 will become a new dominating ``variant of concern''. Currently, no experimental data has been reported about BA.2 and BA.3. We construct a novel algebraic topology-based deep learning model trained with tens of thousands of mutational and deep mutational data to systematically evaluate BA.2's and BA.3's infectivity, vaccine breakthrough capability, and antibody resistance. Our comparative analysis of all main variants namely, Alpha, Beta, Gamma, Delta, Lambda, Mu, BA.1, BA.2, and BA.3, unveils that BA.2 is about 1.5 and 4.2 times as contagious as BA.1 and Delta, respectively. It is also 30% and 17-fold more capable than BA.1 and Delta, respectively, to escape current vaccines. Therefore, we project that Omicron BA.2 is on its path to becoming the next dominating variant. We forecast that like Omicron BA.1, BA.2 will also seriously compromise most existing mAbs, except for sotrovimab developed by GlaxoSmithKline.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的奥密克戎变种由于自然选择,已迅速取代德尔塔变种成为主要的SARS-CoV-2变种,自然选择有利于具有更高传染性和更强疫苗突破能力的变种。奥密克戎有三个谱系或亚变种,即BA.1(B.1.1.529.1)、BA.2(B.1.1.529.2)和BA.3(B.1.1.529.3)。其中,BA.1是目前流行的亚变种。BA.2与BA.1有32个共同突变,但有28个不同突变。BA.3除一个突变外,其大部分突变与BA.1和BA.2相同。研究发现,BA.2能够惊人地再次感染最初感染奥密克戎BA.1的患者。一个重要问题是BA.2或BA.3是否会成为新的主要“关注变种”。目前,尚未有关于BA.2和BA.3的实验数据报道。我们构建了一种基于代数拓扑的新型深度学习模型,用数以万计的突变和深度突变数据进行训练,以系统评估BA.2和BA.3的传染性、疫苗突破能力和抗体抗性。我们对所有主要变种,即阿尔法、贝塔、伽马、德尔塔、拉姆达、缪、BA.1、BA.2和BA.3进行的比较分析表明,BA.2的传染性分别约为BA.1和德尔塔的1.5倍和4.2倍。它逃避现有疫苗的能力也分别比BA.1和德尔塔高30%和17倍。因此,我们预计奥密克戎BA.2正在成为下一个主要变种。我们预测,与奥密克戎BA.1一样,BA.2也将严重影响大多数现有的单克隆抗体,葛兰素史克公司研发的索托维单抗除外。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b4b/8887081/7e8b6db38137/nihpp-rs1362445v1-f0001.jpg

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