Das Nabarun Chandra, Chakraborty Pritha, Bayry Jagadeesh, Mukherjee Suprabhat
Integrative Biochemistry & Immunology Laboratory, Department of Animal Science, Kazi Nazrul University, Asansol 713 340, India.
Department of Biological Sciences & Engineering, Indian Institute of Technology Palakkad, Palakkad 678 623, India.
Antibodies (Basel). 2023 Feb 23;12(1):17. doi: 10.3390/antib12010017.
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 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 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.
刺突蛋白中的突变是新出现的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的主要特征，如阿尔法（B.1.1.7）、贝塔（B.1.351）、伽马（P.1）、德尔塔（B.1.617.2）和德尔塔Plus。奥密克戎（B.1.1.529）是最新出现的变体，其特点是传播性高且能够逃避宿主免疫。最近研发的疫苗和重新利用的药物对奥密克戎毒株的作用有限，因此迫切需要新的治疗方法。在此，我们通过分子对接和分子动力学模拟，探索了12种靶向刺突糖蛋白RBD区域的治疗性单克隆抗体（mAb）对所有在刺突蛋白中携带突变的奥密克戎变体的有效性。我们的证据表明，阿丁替韦单抗、贝鲁替韦单抗和雷加替韦单抗是最有效的单克隆抗体，它们能形成强大的生物物理相互作用并中和大多数奥密克戎变体。考虑到单克隆抗体的疗效，我们将贝鲁替韦单抗的互补决定区3（CDRH3）整合到阿丁替韦单抗的框架内，该嵌合单克隆抗体对所有奥密克戎变体即BA.1、BA.2、BA.2.12.1、BA.4和BA.5表现出更强的结合亲和力。此外，将嵌合单克隆抗体的cDNA克隆到pET30ax中进行重组生产。总之，本研究展示了人源单克隆抗体（贝鲁替韦单抗和阿丁替韦单抗）的候选资格以及设计的嵌合单克隆抗体对治疗奥密克戎感染患者的治疗潜力。
