Andrographolide suppresses SARS-CoV-2 infection by downregulating ACE2 expression: A mechanistic study
Qing Li, Hongmei Lu, Yongdui Ruan, Yuxuan Geng, Zuguo Zhao, Ying Liu, Long Feng, Wentao Guo
Antiviral Therapy, doi:10.1177/13596535241259952
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 dosedependent 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.
Author Contributions YG and HL participated in the experiments, collated data, visualized data, and performed statistical analysis. YR and LF reviewed the manuscript and provided funding. DL was responsible for research oversight. GZ and YL provided suggestions and ideas for manuscript writing. LF and WG contributed to research execution, management, and coordination. All authors contributed to the article and approved the final manuscript version.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study received funding support from several sources, including the Guangdong Provincial Medical Science and Technology Research Fund Project (A2021440), the Guangdong Provincial Bureau of Traditional Chinese Medicine Scientific Research Project (20211220), the Social Science Development Project of Dongguan City (20211800905542), the Guangdong Medical University Scientific Research Project (GDMUQ2021005), and the Discipline Construction Project of Guangdong Medical University (4SG21229GDGFY01).
ORCID iD Wentao Guo https://orcid.org/0000-0002-6194-5687
Supplemental Material Supplemental material for this article is available online.
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