Natural Products from Marine Actinomycete Genus Salinispora Might Inhibit 3CLpro and PLpro Proteins of SARS-CoV-2: An In Silico Evidence

IF 2.1 Q3 MICROBIOLOGY Microbiology Research Pub Date : 2023-11-15 DOI:10.3390/microbiolres14040130
Omkar Pokharkar, G. Zyryanov, M. Tsurkan
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Abstract

Among the oldest marine species on the planet, the genus Salinispora is often encountered inhabiting sediments and other marine creatures in tropical and subtropical marine settings. This bacterial genus produces a plethora of natural products. The purpose of this study was to examine the potential for salinispora-based natural products (NPs) to combat the SARS-CoV-2 virus. The RCSB PDB was used to obtain the crystal structures of proteins 3CLpro and PLpro. All 125 NPs were obtained from online databases. Using Autodock Vina software v1.2.0 the molecular docking process was carried out after the proteins and ligands were prepared. Assessments of binding affinities and interacting amino acids were rigorously examined prior to MD simulations. The docking experiments revealed 35 NPs in total for both 3CLpro and PLpro, with high docking scores ranging from −8.0 kcal/mol to −9.0 kcal/mol. However, a thorough binding residue analyses of all docked complexes filtered nine NPs showing strong interactions with HIS: 41 and CYS: 145 of 3CLpro. Whereas, for PLpro, merely six NPs presented good interactions with residues CYS: 111, HIS: 272, and ASP: 286. Further research was conducted on residue–residue and ligand–residue interactions in both the filtered docked complexes and the Apo-protein structures using the Protein Contacts Atlas website. All complexes were found to be stable in CABS-flex 2.0 MD simulations conducted at various time frames (50, 125, 500, and 1000 cycles). In conclusion, salinaphthoquinone B appears to be the most promising metabolite, based on favorable amino acid interactions forming stable confirmations towards 3CLpro and PLpro enzymes, acting as a dual inhibitor.
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海洋放线菌属 Salinispora 的天然产物可能抑制 SARS-CoV-2 的 3CLpro 和 PLpro 蛋白:硅学证据
Salinispora 属是地球上最古老的海洋物种之一,经常栖息在热带和亚热带海洋环境的沉积物和其他海洋生物中。该细菌属能产生大量天然产品。本研究的目的是考察以盐孢菌为基础的天然产物(NPs)在抗击 SARS-CoV-2 病毒方面的潜力。研究人员利用 RCSB PDB 获得了 3CLpro 和 PLpro 蛋白的晶体结构。所有 125 个 NP 都是从在线数据库中获得的。蛋白质和配体制备完成后,使用 Autodock Vina 软件 v1.2.0 进行了分子对接。在进行 MD 模拟之前,对结合亲和力和相互作用的氨基酸进行了严格的评估。对接实验显示,3CLpro 和 PLpro 共有 35 个 NPs,对接得分较高,从 -8.0 kcal/mol 到 -9.0 kcal/mol。然而,对所有对接复合物的结合残基进行彻底分析后,发现有九种 NPs 与 HIS:41 和 CYS:145。而对于 PLpro,只有 6 种 NP 与残基 CYS:111、HIS:272 和 ASP:284 有良好的相互作用:272 和 ASP: 286。利用蛋白质接触图谱网站对筛选出的对接复合物和 Apo 蛋白结构中的残基-残基和配体-残基相互作用进行了进一步研究。在不同时间范围(50、125、500 和 1000 个周期)进行的 CABS-flex 2.0 MD 模拟中,发现所有复合物都是稳定的。总之,萘醌 B 似乎是最有前途的代谢物,因为它与 3CLpro 和 PLpro 酶的氨基酸相互作用形成了稳定的复合物,起到了双重抑制作用。
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来源期刊
Microbiology Research
Microbiology Research MICROBIOLOGY-
CiteScore
1.90
自引率
6.70%
发文量
62
审稿时长
10 weeks
期刊介绍: Microbiology Research is an international, online-only, open access peer-reviewed journal which publishes original research, review articles, editorials, perspectives, case reports and brief reports to benefit researchers, microbiologists, physicians, veterinarians. Microbiology Research publishes ‘Clinic’ and ‘Research’ papers divided into two different skill and proficiency levels: ‘Junior’ and ‘Professional’. The aim of this four quadrant grid is to encourage younger researchers, physicians and veterinarians to submit their results even if their studies encompass just a limited set of observations or rely on basic statistical approach, yet upholding the customary sound approach of every scientific article.
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