Department of Mathematics, Michigan State University, East Lansing, Michigan 48824, United States.
Spartan Innovations, 325 East Grand River Ave., Suite 355, East Lansing, Michigan 48823, United States.
J Chem Inf Model. 2022 Jan 24;62(2):412-422. doi: 10.1021/acs.jcim.1c01451. Epub 2022 Jan 6.
The latest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron (B.1.1.529) has ushered panic responses around the world due to its contagious and vaccine escape mutations. The essential infectivity and antibody resistance of the SARS-CoV-2 variant are determined by its mutations on the spike (S) protein receptor-binding domain (RBD). However, a complete experimental evaluation of Omicron might take weeks or even months. Here, we present a comprehensive quantitative analysis of Omicron's infectivity, vaccine breakthrough, and antibody resistance. An artificial intelligence (AI) model, which has been trained with tens of thousands of experimental data and extensively validated by experimental results on SARS-CoV-2, reveals that Omicron may be over 10 times more contagious than the original virus or about 2.8 times as infectious as the Delta variant. On the basis of 185 three-dimensional (3D) structures of antibody-RBD complexes, we unveil that Omicron may have an 88% likelihood to escape current vaccines. The U.S. Food and Drug Administration (FDA)-approved monoclonal antibodies (mAbs) from Eli Lilly may be seriously compromised. Omicron may also diminish the efficacy of mAbs from AstraZeneca, Regeneron mAb cocktail, Celltrion, and Rockefeller University. However, its impacts on GlaxoSmithKline's sotrovimab appear to be mild. Our work calls for new strategies to develop the next generation mutation-proof SARS-CoV-2 vaccines and antibodies.
最新的严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)变体奥密克戎(B.1.1.529)由于其传染性和疫苗逃逸突变,在全球范围内引发了恐慌反应。SARS-CoV-2 变体的基本感染力和抗体抗性由其刺突(S)蛋白受体结合域(RBD)上的突变决定。然而,对奥密克戎的完整实验评估可能需要数周甚至数月的时间。在这里,我们对奥密克戎的感染力、疫苗突破和抗体抗性进行了全面的定量分析。一个经过数万个实验数据训练并通过 SARS-CoV-2 的实验结果广泛验证的人工智能(AI)模型表明,奥密克戎的传染性可能比原始病毒高出 10 倍以上,或比 Delta 变体高出约 2.8 倍。基于 185 个抗体-RBD 复合物的三维(3D)结构,我们揭示奥密克戎可能有 88%的可能性逃避当前的疫苗。美国食品和药物管理局(FDA)批准的礼来单抗可能受到严重影响。奥密克戎也可能降低阿斯利康、再生元单抗鸡尾酒、赛尔群和洛克菲勒大学的单抗的疗效。然而,它对葛兰素史克的 sotrovimab 的影响似乎较轻。我们的工作呼吁制定新一代抗突变 SARS-CoV-2 疫苗和抗体的新策略。