Antiviral activity of Humulus lupulus (HOP) aqueous extract against MERS-CoV and SARS-CoV-2: in-vitro and in-silico study

Abstract

Coronaviruses emerged three times in the last two decades and became a source of concern globally. Humulus lupulus plant has been used widely in medical science. Our objective in this study was to determine the effects of the crude extract of H. lupulus in inhibiting MERS-CoV and SARS-CoV-2 viruses’ replication in vitro using Vero E6 cell lines and predict the antiviral activity of its identified compounds against the receptor binding (RBD) protein of both viruses in silico. We determined the concentration of the extract that induced less than 50% cell toxicity (CC₅₀), and the antiviral activity based on IC₅₀ and plaque reduction assay. We used molecular docking simulation to predict the potential of known active compounds in H. lupulus to inhibit the RBD protein. H. lupulus extract showed very low toxicity on Vero E6 cells with CC₅₀= 23.25 µg/µL and antiviral activity toward MERS-CoV and SARS-CoV-2 with IC₅₀= 0.18 and 0.9 µg/µL, respectively. The crude extract showed inhibition rate of 84.6% with MERS-CoV and 80% with SARS-CoV-2. In silico analysis predicted the compounds 5′-prenylxanthohumo, xanthogalenol, dehydrocycloxanthohumol hydrate, 6-prenylnaringenin, isoxanthohumol, catechin gallate, epicatechin gallate, 8-prenylnaringenin and xanthohumol to inhibit MERS-CoV and SARS-CoV-2 invasion of host cells by interfering with viral spike protein and the host cell receptor recognition process. Drug likeness and toxicity risk prediction analysis confirmed their capability as potential drugs. Based on our findings, isolation, purification and testing of the suggested active compounds could lead to novel anti-coronavirus drugs.

Keywords:

• Antiviral activity
• cytotoxicity
• docking
• Humulus lupulus
• virtual screening
• MERS-CoV
• SARS-CoV-2

Acknowledgments

Thamer Ahmed Bouback offers sincere thanks, appreciation, and gratitude to Professor Mohamed Ahmed Ali for providing all necessary logistics facilities for this work. Thamer Ahmed Bouback would also like to thank Dr. Ahmed Kandeil, Brother and instructor, and all researchers and workers at the Center for Scientific Excellence at the National Research Center (NRC), Egypt. Many thanks to Bostan Al Hakeem Shop for giving us advice related to herb usage.

Author contributions

Conceptualization, T.B. and M.A.; methodology, T.B. and A.M.; software, A.A.; validation, A.A., T.B. and M.A.; investigation, T.B., A.M., A.T., Y.M., M.G., and M.A.; writing—original draft preparation, T.B., A.M., A.T., Y.M., M.G., A.A., M.A., and R.B.; writing—review and editing, Y.M., T.B., A.A.; visualization, A.A.; supervision, T.B.

Data availability statement

Data sharing not applicable: All data that support the findings reported in this study are available from the corresponding author [T. B.] upon reasonable request.

Disclosure statement

No potential conflict of interest was reported by the author(s).