Comparative Binding Ability of Human Monoclonal Antibodies against Omicron Variants of SARS-CoV-2: An In Silico Investigation.
Comparative Binding Ability of Human Monoclonal Antibodies against Omicron Variants of SARS-CoV-2: An In Silico Investigation.
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DOI：
10.3390/antib12010017
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发表时间：
2023-02-23
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S蛋白的突变(S)是新出现的SARS-CoV-2变异株的主要特征，如Alpha(B.1.1.7)、Beta(B.1.351)、Gamma(P.1)、Delta(B.1.617.2)和Delta-plus。Omicron(B.1.1.529)是最新的新药，具有高度的传播性和逃避宿主免疫的能力。最近开发的疫苗和重新调整用途的药物对Omicron菌株的作用有限，因此迫切需要新的治疗方法。在这里，我们通过分子对接和分子动力学模拟，探索了12种针对Spike糖蛋白RBD区的治疗性单抗(MAbs)对所有带有Spike蛋白突变的Omicron变体的有效性。我们的电子证据表明，adintivimab、beluDimab和regadanivimab是最有效的单抗，可以形成强烈的生物物理相互作用，并中和大多数Omicron变体。考虑到单抗的有效性，我们将Beludavimab的CDRH3整合到adintrevimab的框架内，它对所有Omicron变体都表现出更强的结合亲和力。BA.1、BA.2、BA.2.12.1、BA.4和BA.5。在此基础上，将嵌合单抗的基因克隆到pET30ax载体中进行重组生产。总之，本研究代表了人源单抗(beludavimab和adintrevimab)的候选以及设计的嵌合单抗治疗奥美康感染患者的潜力。
Mutation(s) in the spike protein is the major characteristic trait of newly emerged SARS-CoV-2 variants such as Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Delta-plus. Omicron (B.1.1.529) is the latest addition and it has been characterized by high transmissibility and the ability to escape host immunity. Recently developed vaccines and repurposed drugs exert limited action on Omicron strains and hence new therapeutics are immediately needed. Herein, we have explored the efficiency of twelve therapeutic monoclonal antibodies (mAbs) targeting the RBD region of the spike glycoprotein against all the Omicron variants bearing a mutation in spike protein through molecular docking and molecular dynamics simulation. Our in silico evidence reveals that adintivimab, beludivimab, and regadanivimab are the most potent mAbs to form strong biophysical interactions and neutralize most of the Omicron variants. Considering the efficacy of mAbs, we incorporated CDRH3 of beludavimab within the framework of adintrevimab, which displayed a more intense binding affinity towards all of the Omicron variants viz. BA.1, BA.2, BA.2.12.1, BA.4, and BA.5. Furthermore, the cDNA of chimeric mAb was cloned in silico within pET30ax for recombinant production. In conclusion, the present study represents the candidature of human mAbs (beludavimab and adintrevimab) and the therapeutic potential of designed chimeric mAb for treating Omicron-infected patients.