School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China.
The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China.
Comput Methods Programs Biomed. 2023 Aug;238:107584. doi: 10.1016/j.cmpb.2023.107584. Epub 2023 May 4.
Patients with rheumatoid arthritis (RA) are more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than healthy population, but there is still no therapeutic strategy available for RA patients with corona virus disease 2019 (COVID-19). Guizhi-Shaoyao-Zhimu decoction (GSZD), Chinese ancient experience decoction, has a significant effect on the treatment of Rheumatism and gout. To prevent RA patients with mild-to-moderate COVID-19 from developing into severe COVID-19, this study explored the potential possibility and mechanism of GSZD in the treatment of this population.
In this study, we used bioinformatic approaches to explore common pharmacological targets and signaling pathways between RA and mild-to-moderate COVID-19, and to assess the potential mechanisms of in the treatment of patients with both diseases. Beside, molecular docking was used to explore the molecular interactions between GSZD and SARS-CoV-2 related proteins.
Results showed that 1183 common targets were found in mild-to-moderate COVID-19 and RA, of which TNF was the most critical target. The crosstalk signaling pathways of the two diseases focused on innate immunity and T cells pathways. In addition, GSZD intervened in RA and mild-to-moderate COVID-19 mainly by regulating inflammation-related signaling pathways and oxidative stress. Twenty hub compounds in GSZD exhibited good binding potential to SARS-CoV-2 spike (S) protein, 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), papain-like protease (PLpro) and human angiotensin-converting enzyme 2 (ACE2), thereby intervening in viral infection, replication and transcription.
This finding provides a therapeutic option for RA patients against mild-to-moderate COVID-19, but further clinical validation is still needed.
类风湿关节炎（RA）患者比健康人群更容易感染严重急性呼吸综合征冠状病毒 2（SARS-CoV-2），但目前针对 COVID-19 合并 RA 的患者仍缺乏有效的治疗策略。桂枝芍药知母汤（GSZD）是一种古老的经验方，对治疗风湿病和痛风有显著疗效。为防止 RA 合并 COVID-19 轻症患者发展为重症 COVID-19，本研究探索了 GSZD 治疗该人群的潜在可能性和机制。
本研究采用生物信息学方法，探讨 RA 和 COVID-19 轻症患者之间的共同药理靶点和信号通路，评估 GSZD 治疗这两种疾病的潜在机制。此外，采用分子对接方法探索 GSZD 与 SARS-CoV-2 相关蛋白的分子相互作用。
结果显示，在 COVID-19 轻症和 RA 中发现了 1183 个共同靶点，其中 TNF 是最关键的靶点。两种疾病的信号通路交叉主要集中在固有免疫和 T 细胞途径。此外，GSZD 主要通过调节炎症相关信号通路和氧化应激来干预 RA 和 COVID-19 轻症。GSZD 中的 20 个关键化合物与 SARS-CoV-2 刺突（S）蛋白、3C 样蛋白酶（3CLpro）、RNA 依赖性 RNA 聚合酶（RdRp）、木瓜蛋白酶样蛋白酶（PLpro）和人血管紧张素转换酶 2（ACE2）具有良好的结合潜力，从而干预病毒感染、复制和转录。
本研究为 COVID-19 合并 RA 患者提供了一种治疗选择，但仍需要进一步的临床验证。
