In silico screening and evaluation of antiviral peptides as inhibitors against ORF9b protein of SARS-CoV-2.

IF 2.6 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

3 Biotech Pub Date : 2024-09-01 Epub Date: 2024-08-06 DOI:10.1007/s13205-024-04032-4

Gaurav Sharma, Prateek Paul, Ananya Dviwedi, Parneet Kaur, Pradeep Kumar, V Kumar Gupta, Saurav Bhaskar Saha, Saurabh Kulshrestha

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引用次数: 0

Abstract

The present study investigated antiviral peptides (AVPs) as inhibitors of SARS-CoV-2 Orf9b protein, a novel target for disrupting the Orf9b-TOM70 complex crucial for viral infection. In silico screening via molecular docking and MD simulations identified AVP1442 and AVP1896 with high binding affinities to Orf9b (- 846.3 kcal mol^-1 and - 820 kcal mol^-1, respectively), comparable to the Orf9b-TOM70 complex (- 810.99 kcal mol^-1). These AVPs interacted with key amino acid residues in Orf9b, including phosphorylation sites. In addition, AVPs also closely interacted with conserved regions in Orf9b. AVP1896 formed a hydrogen bond with Orf9b's threonine at position 84. AVP1442 interacted with Orf9b's leucine at position 15. Favorable Ramachandran plots and compactness during MD simulations for up to 100 ns suggest good stability of formed complexes. These non-toxic AVPs warrant further in vitro and in vivo evaluation, potentially as components of drug cocktails with small molecules or interferon-based therapies.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04032-4.

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作为 SARS-CoV-2 ORF9b 蛋白抑制剂的抗病毒肽的硅学筛选和评估。

本研究调查了作为 SARS-CoV-2 Orf9b 蛋白抑制剂的抗病毒肽（AVPs），Orf9b 蛋白是破坏对病毒感染至关重要的 Orf9b-TOM70 复合物的新靶点。通过分子对接和 MD 模拟进行的硅筛选发现，AVP1442 和 AVP1896 与 Orf9b 的结合亲和力很高（分别为 - 846.3 kcal mol-1 和 - 820 kcal mol-1），与 Orf9b-TOM70 复合物（- 810.99 kcal mol-1）相当。这些 AVP 与 Orf9b 的关键氨基酸残基（包括磷酸化位点）相互作用。此外，AVPs 还与 Orf9b 中的保守区域密切相互作用。AVP1896 与 Orf9b 第 84 位的苏氨酸形成氢键。AVP1442 与 Orf9b 第 15 位的亮氨酸相互作用。在长达 100 ns 的 MD 模拟过程中，良好的拉马钱德兰图和紧凑性表明所形成的复合物具有良好的稳定性。这些无毒的 AVPs 值得进一步进行体外和体内评估，有可能作为小分子鸡尾酒药物或基于干扰素疗法的成分：在线版本包含补充材料，可查阅 10.1007/s13205-024-04032-4。

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来源期刊

3 Biotech Agricultural and Biological Sciences-Agricultural and Biological Sciences (miscellaneous)

CiteScore

6.00

自引率

0.00%

发文量

314

期刊介绍： 3 Biotech publishes the results of the latest research related to the study and application of biotechnology to: - Medicine and Biomedical Sciences - Agriculture - The Environment The focus on these three technology sectors recognizes that complete Biotechnology applications often require a combination of techniques. 3 Biotech not only presents the latest developments in biotechnology but also addresses the problems and benefits of integrating a variety of techniques for a particular application. 3 Biotech will appeal to scientists and engineers in both academia and industry focused on the safe and efficient application of Biotechnology to Medicine, Agriculture and the Environment.