Abstract
Since December 2019, the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused severe pneumonia, a disease named COVID-19, that became pandemic and created an acute threat to public health. The effective therapeutics are in urgent need. Here, we developed a high-content screening for the antiviral candidates using fluorescence-based SARS-CoV-2 nucleoprotein detection in Vero E6 cells coupled with plaque reduction assay. Among 122 Thai natural products, we found that Boesenbergia rotunda extract and its phytochemical compound, panduratin A, exhibited the potent anti-SARS-CoV-2 activity. Treatment with B. rotunda extract and panduratin A after viral infection drastically suppressed SARS-CoV-2 infectivity in Vero E6 cells with IC50 of 3.62 μg/mL (CC50 = 28.06 µg/mL) and 0.81 μΜ (CC50 = 14.71 µM), respectively. Also, the treatment of panduratin A at the pre-entry phase inhibited SARS-CoV-2 infection with IC50 of 5.30 µM (CC50 = 43.47 µM). Our study demonstrated, for the first time, that panduratin A exerts the inhibitory effect against SARS-CoV-2 infection at both pre-entry and post-infection phases. Apart from Vero E6 cells, treatment with this compound was able to suppress viral infectivity in human airway epithelial cells. This result confirmed the potential of panduratin A as the anti-SARS-CoV-2 agent in the major target cells in human. Since B. rotunda is a culinary herb generally grown in China and Southeast Asia, its extract and the purified panduratin A may serve as the promising candidates for therapeutic purposes with economic advantage during COVID-19 situation.
Highlights
In December 2019, multiple severe pneumonia cases emerged in Wuhan, Hubei, C hina[1]
At 48 h after infection, the infected cells were evaluated by fluorescence analysis with the primary antibody specific to NP of SARS-CoV, which was able to cross-react with NP protein of SARS-CoV-2
Panduratin A inhibited SARS-CoV-2 infectivity and replication at both pre-entry and post-infection phases, and its antiviral activity was even more potent than hydroxychloroquine FDA-approved drug currently used for COVID-19 treatment[8,9,10]
Summary
In December 2019, multiple severe pneumonia cases emerged in Wuhan, Hubei, C hina[1]. Due to the urgent scenario and the prospective potential of phytochemicals as an alternative treatment against novel coronavirus as demonstrated by a relevant study on their anti-SARS-CoV activities[21,26], it has prompted us to develop, for the first time, a high-content screening platform to investigate the in vitro potential of locally obtained natural extracts and compounds found in Thai medicinal plants against SARS-CoV-2. From this rationale, we established a high-content screening platform for the antiviral drug candidates by using a fluorescence-based technique in a standard cell line for coronavirus infection, Vero E6. This study demonstrated that Boesenbergia rotunda (fingerroot) extract and its phytochemical, panduratin A, were the promising candidates for a novel treatment against COVID-19
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