Division of Immunobiology and Biomedicine, Sirius University of Science and Technology, Sirius, Krasnodarsky Krai, 354349 Sochi, Russia.
Laboratory of Gene Therapy of Socially Significant Diseases, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia.
Int J Mol Sci. 2023 May 5;24(9):8269. doi: 10.3390/ijms24098269.
The binding properties of synthetic and recombinant peptides derived from N-terminal part of ACE2, the main receptor for SARS-CoV-2, were evaluated. Additionally, the ability of these peptides to prevent virus entry in vitro was addressed using both pseudovirus particles decorated with the S protein, as well as through infection of Vero cells with live SARS-CoV-2 virus. Surprisingly, in spite of effective binding to S protein, all linear peptides of various lengths failed to neutralize the viral infection in vitro. However, the P1st peptide that was chemically "stapled" in order to stabilize its alpha-helical structure was able to interfere with virus entry into ACE2-expressing cells. Interestingly, this peptide also neutralized pseudovirus particles decorated with S protein derived from the Omicron BA.1 virus, in spite of variations in key amino acid residues contacting ACE2.
评估了源自 SARS-CoV-2 的主要受体 ACE2 的 N 端部分的合成肽和重组肽的结合特性。此外，还使用带有 S 蛋白的假病毒颗粒以及用活 SARS-CoV-2 病毒感染 Vero 细胞，研究了这些肽在体外预防病毒进入的能力。令人惊讶的是，尽管与 S 蛋白有效结合，但所有不同长度的线性肽都未能在体外中和病毒感染。然而，为了稳定其α螺旋结构而进行化学“订书钉”的 P1st 肽能够干扰病毒进入表达 ACE2 的细胞。有趣的是，尽管与 ACE2 接触的关键氨基酸残基发生了变化，但该肽也能中和带有 S 蛋白的假病毒颗粒，该 S 蛋白源自奥密克戎 BA.1 病毒。
