An In Silico Approach to Discover Efficient Natural Inhibitors to Tie Up Epstein-Barr Virus Infection.

IF 3.3 3区医学 Q2 MICROBIOLOGY Pathogens Pub Date : 2024-10-25 DOI:10.3390/pathogens13110928

Ayan Das, Mumtaza Mumu, Tanjilur Rahman, Md Abu Sayeed, Md Mazharul Islam, John I Alawneh, Mohammad Mahmudul Hassan

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Abstract

Epstein-Barr virus (EBV), also known as human herpesvirus 4, is a member of the herpes virus family. EBV is a widespread virus and causes infectious mononucleosis, which manifests with symptoms such as fever, fatigue, lymphadenopathy, splenomegaly, and hepatomegaly. Additionally, EBV is associated with different lymphocyte-associated non-malignant, premalignant, and malignant diseases. So far, no effective treatment or therapeutic drug is known for EBV-induced infections and diseases. This study investigated natural compounds that inhibit EBV glycoprotein L (gL) and block EBV fusion in host cells. We utilised computational approaches, including molecular docking, in silico ADMET analysis, and molecular dynamics simulation. We docked 628 natural compounds against gL and identified the four best compounds based on binding scores and pharmacokinetic properties. These four compounds, with PubChem CIDs 4835509 (CHx-HHPD-Ac), 2870247 (Cyh-GlcNAc), 21206004 (Hep-HHPD-Ac), and 51066638 (Und-GlcNAc), showed several interactions with EBV gL. However, molecular dynamics simulations indicated that the protein-ligand complexes of CID: 4835509 (CHx-HHPD-Ac) and CID: 2870247 (Cyh-GlcNAc) are more stable than those of the other two compounds. Therefore, CIDs 4835509 and 2870247 (Cyh-GlcNAc) may be potent natural inhibitors of EBV infection. These findings can open a new way for effective drug design against EBV and its associated infections and diseases.

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一种发现高效天然抑制剂的硅学方法，用于抑制 Epstein-Barr 病毒感染。

爱泼斯坦-巴尔病毒（EBV）又称人类疱疹病毒 4，是疱疹病毒家族的一员。EBV 是一种广泛传播的病毒，可引起传染性单核细胞增多症，表现为发热、乏力、淋巴结肿大、脾脏肿大和肝脏肿大等症状。此外，EBV 还与不同的淋巴细胞相关的非恶性、恶性前和恶性疾病有关。迄今为止，还没有针对 EBV 引起的感染和疾病的有效治疗方法或治疗药物。本研究调查了抑制 EBV 糖蛋白 L（gL）和阻止 EBV 在宿主细胞中融合的天然化合物。我们采用了计算方法，包括分子对接、默克 ADMET 分析和分子动力学模拟。我们将 628 种天然化合物与 gL 进行了对接，并根据结合得分和药代动力学特性确定了四种最佳化合物。这四种化合物的 PubChem CID 分别为 4835509（CHx-HHPD-Ac）、2870247（Cyh-GlcNAc）、21206004（Hep-HHPD-Ac）和 51066638（Und-GlcNAc），它们与 EBV gL 发生了多次相互作用。然而，分子动力学模拟表明，CID: 4835509（CHx-HHPD-Ac）和 CID: 2870247（Cyh-GlcNAc）的蛋白质配体复合物比其他两种化合物更稳定。因此，CID 4835509 和 2870247（Cyh-GlcNAc）可能是有效的天然 EBV 感染抑制剂。这些发现将为针对 EBV 及其相关感染和疾病的有效药物设计开辟一条新途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pathogens Medicine-Immunology and Allergy

CiteScore

6.40

自引率

8.10%

发文量

1285

审稿时长

17.75 days

期刊介绍： Pathogens (ISSN 2076-0817) publishes reviews, regular research papers and short notes on all aspects of pathogens and pathogen-host interactions. There is no restriction on the length of the papers. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible. Full experimental and/or methodical details must be provided for research articles.