Chen Jiahui, Wei Guo-Wei
Department of mathematics, Michigan State University, East Lansing, MI 48823, USA.
Commun Inf Syst. 2022;22(3):339-361. doi: 10.4310/cis.2022.v22.n3.a3. Epub 2022 Jul 22.
Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have compromised existing vaccines and posed a grand challenge to coronavirus disease 2019 (COVID-19) prevention, control, and global economic recovery. For COVID-19 patients, one of the most effective COVID-19 medications is monoclonal antibody (mAb) therapies. The United States Food and Drug Administration (U.S. FDA) has given the emergency use authorization (EUA) to a few mAbs, including those from Regeneron, Eli Elly, etc. However, they are also undermined by SARS-CoV-2 mutations. It is imperative to develop effective mutation-proof mAbs for treating COVID-19 patients infected by all emerging variants and/or the original SARS-CoV-2. We carry out a deep mutational scanning to present the blueprint of such mAbs using algebraic topology and artificial intelligence (AI). To reduce the risk of clinical trial-related failure, we select five mAbs either with FDA EUA or in clinical trials as our starting point. We demonstrate that topological AI-designed mAbs are effective for variants of concerns and variants of interest designated by the World Health Organization (WHO), as well as the original SARS-CoV-2. Our topological AI methodologies have been validated by tens of thousands of deep mutational data and their predictions have been confirmed by results from tens of experimental laboratories and population-level statistics of genome isolates from hundreds of thousands of patients.
新型严重急性呼吸综合征冠状病毒2(SARS-CoV-2)变种削弱了现有疫苗的效力,对2019冠状病毒病(COVID-19)的预防、控制及全球经济复苏构成了巨大挑战。对于COVID-19患者而言,最有效的COVID-19药物之一是单克隆抗体(mAb)疗法。美国食品药品监督管理局(U.S. FDA)已授予包括再生元、礼来等公司生产的几种单克隆抗体紧急使用授权(EUA)。然而,它们也受到SARS-CoV-2突变的影响。开发有效的抗突变单克隆抗体以治疗所有新出现变种和/或原始SARS-CoV-2感染的COVID-19患者势在必行。我们利用代数拓扑和人工智能(AI)进行深度突变扫描,以呈现此类单克隆抗体的蓝图。为降低临床试验相关失败的风险,我们选择了五种已获得FDA紧急使用授权或正在进行临床试验的单克隆抗体作为起点。我们证明,拓扑人工智能设计的单克隆抗体对世界卫生组织(WHO)指定的关注变种和感兴趣变种以及原始SARS-CoV-2均有效。我们的拓扑人工智能方法已通过数万个深度突变数据得到验证,其预测结果已被数十个实验实验室的结果以及来自数十万患者的基因组分离株的群体水平统计数据所证实。