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合成肽对严重急性呼吸综合征冠状病毒2的中和作用

Neutralizing Effect of Synthetic Peptides toward SARS-CoV-2.

作者信息

Souza Pedro F N, vanTilburg Maurício F, Mesquita Felipe P, Amaral Jackson L, Lima Luina B, Montenegro Raquel C, Lopes Francisco E S, Martins Rafael X, Vieira Leonardo, Farias Davi F, Monteiro-Moreira Ana C O, Freitas Cleverson D T, Bezerra Arnaldo S, Guedes Maria I F, Castelo-Branco Débora S C M, Oliveira Jose T A

机构信息

Department of Biochemistry and Molecular Biology, Federal University of Ceará, Av Mister Hull, S/n-Pici, P.O. Box 60440-593, Fortaleza, Ceará 60020-181, Brazil.

Drug Research and Development Center, Department of Physiology and Pharmacology, Federal University of Ceará, Rua Coronel Nunes de Melo 100, P.O. Box 60430-275, Fortaleza, Ceará 60020-181, Brazil.

出版信息

ACS Omega. 2022 Apr 28;7(18):16222-16234. doi: 10.1021/acsomega.2c02203. eCollection 2022 May 10.

Abstract

The outbreak caused by SARS-CoV-2 has taken many lives worldwide. Although vaccination has started, the development of drugs to either alleviate or abolish symptoms of COVID-19 is still necessary. Here, four synthetic peptides were assayed regarding their ability to protect Vero E6 cells from SARS-CoV-2 infection and their toxicity to human cells and zebrafish embryos. All peptides had some ability to protect cells from infection by SARS-CoV-2 with the D614G mutation. Molecular docking predicted the ability of all peptides to interact with and induce conformational alterations in the spike protein containing the D614G mutation. PepKAA was the most effective peptide, by having the highest docking score regarding the spike protein and reducing the SARS-CoV-2 plaque number by 50% (EC) at a concentration of 0.15 mg mL. Additionally, all peptides had no toxicity to three lines of human cells as well as to zebrafish larvae and embryos. Thus, these peptides have potential activity against SARS-CoV-2, making them promising to develop new drugs to inhibit cell infection by SARS-CoV-2.

摘要

由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的疫情已在全球夺走许多生命。尽管疫苗接种已经开始,但研发缓解或消除新冠肺炎症状的药物仍然很有必要。在此,对四种合成肽进行了检测,评估它们保护非洲绿猴肾细胞(Vero E6)免受SARS-CoV-2感染的能力以及它们对人类细胞和斑马鱼胚胎的毒性。所有肽都具有一定能力保护细胞免受携带D614G突变的SARS-CoV-2感染。分子对接预测了所有肽与含有D614G突变的刺突蛋白相互作用并诱导其构象改变的能力。肽KAA是最有效的肽,它与刺突蛋白的对接分数最高,并且在浓度为0.15 mg/mL时可使SARS-CoV-2蚀斑数量减少50%(半数有效浓度)。此外,所有肽对三株人类细胞系以及斑马鱼幼体和胚胎均无毒性。因此,这些肽具有抗SARS-CoV-2的潜在活性,有望开发出抑制SARS-CoV-2感染细胞的新药。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aac/9097211/b0f613b1802b/ao2c02203_0002.jpg

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