Anti-SARS-CoV-2 Activity and Inhibition of ACE2 and TMPRSS2 Expression of Ya Prasa Pro Yai, Ya Ha Rak and Ya Chanthalila Traditional Drug Formulas
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Abstract
Introduction and objective: Coronavirus disease 2019 (COVID-19) is caused by the SARS-CoV-2. Some Thai traditional drug formulas have been prescribed in Thailand to alleviate symptoms caused by the virus. The objective of this study was to investigate the anti-SARS-CoV-2 properties of Ya Prasa Pro Yai (PSP), Ya Ha Rak (Y5R) and Ya Chanthalila (CTL) drug formulas used as antipyretic in Thai traditional medicine.
Methods: The drugs were extracted and screened for anti-SARS-CoV-2 activity using plaque reduction assay. The extracts were further investigated for ACE2 and TMPRSS2 enzymatic inhibition and gene expression assays of several host-target molecules in Calu-3 cells.
Results: PSP, Y5R, and CTL traditional drug formulas were found to have shown inhibitory activities against SARS-CoV-2 at 45.6%, 45.6% and 50.1%, respectively, at the concentration of 5,000 µg/mL. CTL also significantly inhibited (71.2%) the main human receptor ACE2 at the concentration of 2,000 µg/mL, which was higher than both PSP and Y5R extracts and demonstrated TMPRSS2 enzymatic inhibition in a dose-dependent manner. CTL also significantly down-regulated the expression of ACE2, but not TMPRSS2, PIKfyve and cathepsin L in Calu-3 cells.
Discussion: The Thai traditional drug formulas reported here provided anti-SARS-CoV-2 activities. Testing of the Anti-viral properties of the three preparations at 5 mg/mL did not reveal significant differences. However, CTL showed more anti-viral activity than others consistent with the previous study that the effect may be from E. longifolia Jack, one of the components of the formulation. CTL showed inhibition of ACE2 and TMPRSS2 enzymes in dose-dependent manner compared to the controls. Moreover, the CTL preparation also demonstrated a significant down-regulation of ACE2 gene expression on calu-3, human lung cell lines which are the mechanisms inhibiting the entry into the cells in the early phase of infection.
Conclusion: Ya Prasa Pro Yai (PSP), Ya Ha Rak (Y5R) and Ya Chanthalila (CTL) herbal drug formulas were effective against SARS-CoV-2. Ya Chanthalila should be especially reconsidered as the first-line drug in clinical trials, which can not only reduce fever, but also limit SARS-CoV-2 spreading in the patient.
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