Laboratory for Nanomedicine, Division of Biological and Environmental Science and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
KAUST Smart Health Initiative (KSHI), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
Biomed Res Int. 2023 Oct 13;2023:3892370. doi: 10.1155/2023/3892370. eCollection 2023.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has greatly affected all aspect of life. Although several vaccines and pharmaceuticals have been developed against SARS-CoV-2, the emergence of mutated variants has raised several concerns. The angiotensin-converting enzyme (ACE2) receptor cell entry mechanism of this virus has not changed despite the vast mutation in emerging variants. Inhibiting the spike protein by which the virus identifies the host ACE2 receptor is a promising therapeutic countermeasure to keep pace with rapidly emerging variants. Here, we synthesized two ACE2-derived peptides, P1 and P25, to target and potentially inhibit SARS-CoV-2 cell entry. These peptides were evaluated using pseudoviruses that contained the SARS-CoV-2 original spike protein, the Delta-mutated spike protein, or the Omicron spike protein. An in silico investigation was also done for these peptides to evaluate the interaction of the synthesized peptides and the SARS-CoV-2 variants. The P25 peptide showed a promising inhibition potency against the tested pseudoviruses and an even higher inhibition against the Omicron variant. The IC of the Omicron variant was 60.8 M, while the ICs of the SARS-CoV-2 original strain and the Delta variant were 455.2 M and 546.4 M, respectively. The experiments also showed that the amino acid composition design and structure of P25 boosted the interaction with the spike protein. These findings suggest that ACE2-derived peptides, such as P25, have the potential to inhibit SARS-CoV-2 cell entry in vitro. However, further in vivo studies are needed to confirm their therapeutic efficacy against emerging variants.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）大流行极大地影响了生活的方方面面。尽管已经针对 SARS-CoV-2 开发了几种疫苗和药物，但出现的突变变体引起了人们的关注。尽管新出现的变体中存在大量突变，但该病毒的血管紧张素转换酶（ACE2）受体细胞进入机制并未改变。抑制病毒识别宿主 ACE2 受体的刺突蛋白是一种有前途的治疗对策，可以跟上快速出现的变体。在这里，我们合成了两种 ACE2 衍生肽，P1 和 P25，以靶向并可能抑制 SARS-CoV-2 细胞进入。使用含有 SARS-CoV-2 原始刺突蛋白、Delta 突变刺突蛋白或奥密克戎刺突蛋白的假病毒评估了这些肽。还对这些肽进行了计算机模拟研究，以评估合成肽与 SARS-CoV-2 变体的相互作用。P25 肽对测试的假病毒表现出有希望的抑制效力，对奥密克戎变体的抑制作用更高。奥密克戎变体的 IC 为 60.8 μM，而 SARS-CoV-2 原始株和 Delta 变体的 IC 分别为 455.2 μM 和 546.4 μM。实验还表明，P25 的氨基酸组成设计和结构增强了与刺突蛋白的相互作用。这些发现表明，ACE2 衍生肽，如 P25，有可能在体外抑制 SARS-CoV-2 细胞进入。然而，需要进一步的体内研究来确认它们对新出现的变体的治疗效果。
