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短杆菌肽 S 和蜂毒素:治疗 SARS-CoV-2 感染的潜在抗病毒治疗性肽。

Gramicidin S and melittin: potential anti-viral therapeutic peptides to treat SARS-CoV-2 infection.

机构信息

CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Telangana, 500007, India.

出版信息

Sci Rep. 2022 Mar 2;12(1):3446. doi: 10.1038/s41598-022-07341-x.

DOI:10.1038/s41598-022-07341-x
PMID:35236909
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8891299/
Abstract

The COVID19 pandemic has led to multipronged approaches for treatment of the disease. Since de novo discovery of drugs is time consuming, repurposing of molecules is now considered as one of the alternative strategies to treat COVID19. Antibacterial peptides are being recognized as attractive candidates for repurposing to treat viral infections. In this study, we describe the anti-SARS-CoV-2 activity of the well-studied antibacterial peptides gramicidin S and melittin obtained from Bacillus brevis and bee venom respectively. The EC values for gramicidin S and melittin were 1.571 µg and 0.656 µg respectively based on in vitro antiviral assay. Significant decrease in the viral load as compared to the untreated group with no/very less cytotoxicity was observed. Both the peptides treated to the SARS-CoV-2 infected Vero cells showed viral clearance from 12 h onwards with a maximal viral clearance after 24 h post infection. Proteomics analysis indicated that more than 250 proteins were differentially regulated in the gramicidin S and melittin treated SARS-CoV-2 infected Vero cells against control SARS-CoV-2 infected Vero cells after 24 and 48 h post infection. The identified proteins were found to be associated in the metabolic and mRNA processing of the Vero cells post-treatment and infection. Both these peptides could be attractive candidates for repurposing to treat SARS-CoV-2 infection.

摘要

新冠疫情促使人们采用多种方法治疗该疾病。由于新药研发耗时较长,因此目前人们认为重新利用现有分子是治疗 COVID-19 的一种替代策略。抗菌肽正逐渐成为治疗病毒感染的候选药物。在这项研究中,我们描述了来自短芽孢杆菌和蜜蜂毒液的两种研究较为充分的抗菌肽:短杆菌肽 S 和蜂毒素抗 SARS-CoV-2 的活性。基于体外抗病毒试验,短杆菌肽 S 和蜂毒素的 EC 值分别为 1.571µg 和 0.656µg。与未处理组相比,观察到病毒载量显著下降,同时细胞毒性很低或几乎没有。用这两种肽处理感染 SARS-CoV-2 的 Vero 细胞后,从 12 小时开始即可清除病毒,在感染后 24 小时达到最大清除率。蛋白质组学分析表明,与对照 SARS-CoV-2 感染的 Vero 细胞相比,在感染 SARS-CoV-2 的 Vero 细胞中,短杆菌肽 S 和蜂毒素处理后 24 小时和 48 小时,有 250 多种蛋白质的表达存在差异。鉴定出的蛋白质与 Vero 细胞在治疗和感染后的代谢和 mRNA 加工有关。这两种肽都可能是重新用于治疗 SARS-CoV-2 感染的有吸引力的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bc8/8891299/e5a019db6010/41598_2022_7341_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bc8/8891299/a73390669c90/41598_2022_7341_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bc8/8891299/b8e0130758f1/41598_2022_7341_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bc8/8891299/3d30d5896ca7/41598_2022_7341_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bc8/8891299/e5a019db6010/41598_2022_7341_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bc8/8891299/a73390669c90/41598_2022_7341_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bc8/8891299/bd0fc5fc86ba/41598_2022_7341_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bc8/8891299/8b9f402a3da1/41598_2022_7341_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bc8/8891299/b8e0130758f1/41598_2022_7341_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bc8/8891299/3d30d5896ca7/41598_2022_7341_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bc8/8891299/e5a019db6010/41598_2022_7341_Fig6_HTML.jpg

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