Andrographolide suppresses SARS-CoV-2 infection by downregulating ACE2 expression: A mechanistic study.

IF 1.3 4区 医学 Q4 INFECTIOUS DISEASES
Qing Li, Hongmei Lu, Yongdui Ruan, Yuxuan Geng, Zuguo Zhao, Ying Liu, Long Feng, Wentao Guo
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引用次数: 0

Abstract

Angiotensin-converting enzyme 2 (ACE2) is the receptor that enables SARS-CoV-2 to invade host cells. Previous studies have reported that reducing ACE2 expression may have an anti-SARS-CoV-2 effect. In this study, we constructed a pGL4.10-F2-ACE2 vector with double luciferase genes (firefly and Renilla luciferase) under the control of the ACE2 promoter and used it to screen compounds from Chinese traditional medicinal herbs (CTMHs) that can inhibit ACE2 transcription in human cells. We transfected HEK293T cells with pGL4.10-F2-ACE2 and treated them with CTMH compounds and then measured fluorescence to evaluate the indirect inhibition of ACE2 transcription. Out of 37 compounds tested, andrographolide demonstrated a dose-dependent inhibition of ACE2 transcription. We further confirmed by RT-qPCR and Western blot assays that andrographolide also reduced ACE2 expression in BEAS-2B cells in a dose-dependent manner. Moreover, pseudovirus infection assays in BEAS-2B cells demonstrated that andrographolide can inhibit SARS-CoV-2 infection in a dose-dependent manner. These results suggest that andrographolide has potential anti-SARS-CoV-2 activity and could be a candidate drug for COVID-19 prevention and treatment.

穿心莲内酯通过下调 ACE2 表达抑制 SARS-CoV-2 感染:机理研究
血管紧张素转换酶 2(ACE2)是使 SARS-CoV-2 侵入宿主细胞的受体。以前的研究报道,减少 ACE2 的表达可能具有抗 SARS-CoV-2 的作用。在本研究中,我们构建了一个pGL4.10-F2-ACE2载体,该载体含有双荧光素酶基因(萤火虫荧光素酶和雷尼拉荧光素酶),受ACE2启动子控制。我们用pGL4.10-F2-ACE2转染了HEK293T细胞,并用CTMH化合物处理它们,然后测量荧光来评估对ACE2转录的间接抑制作用。在测试的 37 种化合物中,穿心莲内酯对 ACE2 转录具有剂量依赖性抑制作用。我们还通过 RT-qPCR 和 Western 印迹检测进一步证实,穿心莲内酯也能以剂量依赖的方式降低 BEAS-2B 细胞中 ACE2 的表达。此外,在 BEAS-2B 细胞中进行的假病毒感染实验表明,穿心莲内酯能以剂量依赖性方式抑制 SARS-CoV-2 感染。这些结果表明穿心莲内酯具有潜在的抗 SARS-CoV-2 活性,可作为 COVID-19 预防和治疗的候选药物。
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来源期刊
Antiviral Therapy
Antiviral Therapy 医学-病毒学
CiteScore
2.60
自引率
8.30%
发文量
35
审稿时长
4-8 weeks
期刊介绍: Antiviral Therapy (an official publication of the International Society of Antiviral Research) is an international, peer-reviewed journal devoted to publishing articles on the clinical development and use of antiviral agents and vaccines, and the treatment of all viral diseases. Antiviral Therapy is one of the leading journals in virology and infectious diseases. The journal is comprehensive, and publishes articles concerning all clinical aspects of antiviral therapy. It features editorials, original research papers, specially commissioned review articles, letters and book reviews. The journal is aimed at physicians and specialists interested in clinical and basic research.
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