Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad, Haryana, India.
PLoS Pathog. 2022 Dec 12;18(12):e1010994. doi: 10.1371/journal.ppat.1010994. eCollection 2022 Dec.
The emergence of new variants of SARS-CoV-2 necessitates unremitting efforts to discover novel therapeutic monoclonal antibodies (mAbs). Here, we report an extremely potent mAb named P4A2 that can neutralize all the circulating variants of concern (VOCs) with high efficiency, including the highly transmissible Omicron. The crystal structure of the P4A2 Fab:RBD complex revealed that the residues of the RBD that interact with P4A2 are a part of the ACE2-receptor-binding motif and are not mutated in any of the VOCs. The pan coronavirus pseudotyped neutralization assay confirmed that the P4A2 mAb is specific for SARS-CoV-2 and its VOCs. Passive administration of P4A2 to K18-hACE2 transgenic mice conferred protection, both prophylactically and therapeutically, against challenge with VOCs. Overall, our data shows that, the P4A2 mAb has immense therapeutic potential to neutralize the current circulating VOCs. Due to the overlap between the P4A2 epitope and ACE2 binding site on spike-RBD, P4A2 may also be highly effective against a number of future variants.
SARS-CoV-2 的新变体的出现需要不懈努力来发现新的治疗性单克隆抗体（mAb）。在这里，我们报告了一种名为 P4A2 的极其有效的 mAb，它可以高效中和所有流行的变异株（VOCs），包括高度传播的奥密克戎。P4A2 Fab：RBD 复合物的晶体结构表明，与 P4A2 相互作用的 RBD 残基是 ACE2 受体结合基序的一部分，在任何 VOC 中都没有发生突变。泛冠状病毒假型中和测定证实，P4A2 mAb 是特异性针对 SARS-CoV-2 及其 VOCs 的。将 P4A2 被动给药给 K18-hACE2 转基因小鼠，在预防和治疗方面都能提供针对 VOC 挑战的保护。总的来说，我们的数据表明，P4A2 mAb 具有中和当前流行的 VOCs 的巨大治疗潜力。由于 P4A2 表位与 Spike-RBD 上的 ACE2 结合位点重叠，P4A2 可能对许多未来的变体也非常有效。
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