Galangal-Cinnamon Spice Mixture Blocks the Coronavirus Infection Pathway through Inhibition of SARS-CoV-2 MPro, Three HCoV-229E Targets; Quantum-Chemical Calculations Support In Vitro Evaluation

Doaa G El-Hosari; Wesam M Hussein; Marwa O Elgendy; Sara O Elgendy; Ahmed R N Ibrahim; Alzhraa M Fahmy; Afnan Hassan; Fatma Alzahraa Mokhtar; Modather F Hussein; Mohamed E A Abdelrahim; Eman G Haggag

doi:10.3390/ph16101378

Galangal-Cinnamon Spice Mixture Blocks the Coronavirus Infection Pathway through Inhibition of SARS-CoV-2 M^Pro, Three HCoV-229E Targets; Quantum-Chemical Calculations Support In Vitro Evaluation

Pharmaceuticals (Basel). 2023 Sep 28;16(10):1378. doi: 10.3390/ph16101378.

Authors

Affiliations

¹ Pharmacognosy Department, Faculty of Pharmacy, Helwan University, Cairo 11795, Egypt.
² Department of Clinical Pharmacy, Beni-Suef University Hospitals, Faculty of Medicine, Beni-Suef University, Beni-Suef 62521, Egypt.
³ Department of Clinical Pharmacy, Faculty of Pharmacy, Nahda University (NUB), Beni-Suef 62513, Egypt.
⁴ Clinical and Chemical Pathology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef 62521, Egypt.
⁵ Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia.
⁶ Tropical Medicine and Infectious Diseases Department, Faculty of Medicine, Beni-Suef University, Beni-Suef 62521, Egypt.
⁷ Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, Cairo 12578, Egypt.
⁸ Department of Pharmacognosy, Faculty of Pharmacy, El Saleheya El Gadida University, El Saleheya El Gadida 44813, Egypt.
⁹ Chemistry Department, Collage of Science, Jouf University, P.O. Box 2014, Sakaka 72388, Saudi Arabia.
¹⁰ Chemistry Department, Faculty of Science, Al-Azhar University, Asyut Branch, Assiut 71524, Egypt.
¹¹ Clinical Pharmacy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62521, Egypt.

Abstract

Natural products such as domestic herbal drugs which are easily accessible and cost-effective can be used as a complementary treatment in mild and moderate COVID-19 cases. This study aimed to detect and describe the efficiency of phenolics detected in the galangal-cinnamon mixture in the inhibition of SARS-CoV-2's different protein targets. The potential antiviral effect of galangal-cinnamon aqueous extract (GCAE) against Low Pathogenic HCoV-229E was assessed using cytopathic effect inhibition assay and the crystal violet method. Low Pathogenic HCoV-229E was used as it is safer for in vitro laboratory experimentation and due to the conformation and the binding pockets similarity between HCoV-229E and SARS-CoV-2 M^Pro. The GCAE showed a significant antiviral effect against HCoV-229E (IC₅₀ 15.083 µg/mL). Twelve phenolic compounds were detected in the extract with ellagic, cinnamic, and gallic acids being the major identified phenolic acids, while rutin was the major identified flavonoid glycoside. Quantum-chemical calculations were made to find molecular properties using the DFT/B3LYP method with 6-311++G(2d,2p) basis set. Quantum-chemical values such as EHOMO, ELUMO, energy gap, ionization potential, chemical hardness, softness, and electronegativity values were calculated and discussed. Phenolic compounds detected by HPLC-DAD-UV in the GCAE were docked into the active site of 3 HCoV-229E targets (PDB IDs. 2ZU2, 6U7G, 7VN9, and 6WTT) to find the potential inhibitors that block the Coronavirus infection pathways from quantum and docking data for these compounds. There are good adaptations between the theoretical and experimental results showing that rutin has the highest activity against Low Pathogenic HCoV-229E in the GCAE extract.

Keywords: SARS-CoV-2 MPro; antiviral assay; galangal–cinnamon aqueous extract; phenolic compounds; quantum-chemical methods.

Grants and funding

This research was funded by the Deanship of Scientific Research at King Khalid University through a large group Research Project under grant number (RGP2/145/44).