1. Graduate Institute of Biomedical Sciences, China Medical University, Taichung 406040, Taiwan.
2. Department of Cosmeceutics, China Medical University, Taichung 406040, Taiwan.
3. Institute of New Drug Development, China Medical University, Taichung 406040, Taiwan.
4. Research Center for Cancer Biology, China Medical University, Taichung 406040, Taiwan.
5. International Master's Program of Biomedical Sciences, China Medical University, Taichung 406040, Taiwan.
6. Department of Medical Research, China Medical University Hospital, Taichung 404332, Taiwan.
7. Department of Biological Science and Technology, China Medical University, Taichung 406040, Taiwan.
8. Biomedical Translation Research Center (BioTReC), Academia Sinica, Taipei 115024, Taiwan.
9. Center for Molecular Medicine, China Medical University Hospital, China Medical University, Taichung 404332, Taiwan.
10. Department of Biotechnology, Asia University, Taichung, 41354 Taiwan.
In the current climate, many countries are in dire need of effective preventive methods to curb the Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) pandemic. The purpose of this research is to screen and explore natural plant extracts that have the potential to against SARS-CoV-2 and provide alternative options for SARS-CoV-2 prevention and hand sanitizer or spray-like disinfectants. We first used Spike-ACE2 ELISA and TMPRSS2 fluorescence resonance energy transfer (FRET) assays to screen extracts from agricultural by-products from Taiwan with the potential to impede SARS-CoV-2 infection. Next, the SARS-CoV-2 pseudo-particles (Vpp) infection assay was tested to validate the effectiveness. We identified an extract from coffee leaf (Coffea Arabica), a natural plant that effectively inhibited wild-type SARS-CoV-2, and five Variants of Concern (Alpha, Beta, Gamma, Delta, and Omicron strain) from entering host cells. In an attempt to apply coffee leaf extract for hand sanitizer or spray-like disinfectants, we designed a skin-like gelatin membrane experiment. We showed that the high concentration of coffee leaf extract on the skin surface could block SARS-CoV-2 into cells more potently than 75% Ethanol, a standard disinfectant to inactivate SARS-CoV-2. Finally, LC-HRMS analysis was used to identify compounds such as caffeine, chlorogenic acid (CGA), quinic acid, and mangiferin that are associated with an anti-SARS-CoV-2 activity. Our results demonstrated that coffee leaf extract, an agricultural by-product effectively inhibits SARS-CoV-2 Vpp infection through an ACE2-dependent mechanism and may be utilized to develop products against SARS-CoV-2 infection.
Keywords: Coffee leaf, SARS-CoV-2, Spike, ACE2, skin