Virtual Screening Approaches Towards the Discovery of Toll-like Receptor 7 (TLR7) Antagonists for the Management of Rheumatoid Arthritis During COVID Infection.

IF 1.2 Q4 RHEUMATOLOGY

Current rheumatology reviews Pub Date : 2025-04-09 DOI:10.2174/0115733971351438250220063238

Thangavelu Prabha, Saravanan Thangavelu, Dakshinesh Parameswaran, M K Kathiravan, Hemalatha Selvaraj, Chaitanya M V N L, S Sri Bhuvaneswari, Jubie Selvaraj

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引用次数: 0

Abstract

Background: Rheumatoid arthritis(RA) patients prompt to have high level of TLR7, when coronavirus (CoV-2) infect to these patients, further the level of TLR7 cloud be upregulated and leads to severe condition of RA. Since, some TLR7 antagonists targeting the TLR7 protein are in the clinical trials, but yet to reach the market, and many lead to serious toxicities.

Objective: So, we have framed a hypothesis to discover the TLR7 antagonist that may inhibit to the upregulation of TLR 7 in RA patients during the CoV-2infection via virtual screening meth-odology.

Methods: Here we have focused to discover some novel TLR7 inhibitors from the ZINC data-base,which may effectively inhibit TLR7. Series of virtual screening analysis lead to the discov-ery of three active hits.

Results: Among these three molecules, ZINC95412580 had a highest binding energy of -15.4273 kcal/mol against the TLR7 protein (PDB Id: 6LW1) that also showed the maximum interactions within the binding pocket.

Conclusion: Thus, the compounds discovered through the use of various software can possibly be used for the management of rheumatoid arthritis during and after COVID infection. Hence, we can conclude that these molecules might be served as the inhibitors of TLR7 upregulation.

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发现toll样受体7 （TLR7）拮抗剂治疗类风湿性关节炎在COVID感染期间的虚拟筛选方法

背景：类风湿性关节炎（RA）患者提示TLR7水平较高，当冠状病毒（CoV-2）感染这些患者时，TLR7水平可能进一步上调，导致RA病情加重。因此，一些靶向TLR7蛋白的TLR7拮抗剂正处于临床试验阶段，但尚未进入市场，许多拮抗剂会导致严重的毒性。目的：因此，我们提出了一个假设，通过虚拟筛选方法，发现在cov -2感染期间可能抑制RA患者TLR7上调的TLR7拮抗剂。方法：重点从ZINC数据库中发现可能有效抑制TLR7的新型TLR7抑制剂。一系列的虚拟筛选分析导致发现三个活跃的命中。结果：ZINC95412580对TLR7蛋白（PDB Id: 6LW1）的结合能最高，为-15.4273 kcal/mol，且在结合袋内的相互作用最大。结论：因此，通过使用各种软件发现的化合物可能用于COVID感染期间和之后的类风湿关节炎治疗。因此，我们可以得出结论，这些分子可能是TLR7上调的抑制剂。

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

Current rheumatology reviews RHEUMATOLOGY-

CiteScore

2.30

自引率

0.00%

发文量

期刊介绍： Current Rheumatology Reviews publishes frontier reviews on all the latest advances on rheumatology and its related areas e.g. pharmacology, pathogenesis, epidemiology, clinical care, and therapy. The journal"s aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all researchers and clinicians in rheumatology.