Naturally Available Flavonoid Aglycones as Potential Antiviral Drug Candidates against SARS-CoV-2
Ahmed A. Al-Karmalawy,
Mai M. Farid,
Ahmed Mostafa,
Alia Y. Ragheb,
Sara H. Mahmoud,
Mahmoud Shehata,
Noura M. Abo Shama,
Mohamed GabAllah,
Gomaa Mostafa-Hedeab,
Mona M. Marzouk
Affiliations
Ahmed A. Al-Karmalawy
Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt
Mai M. Farid
Department of Phytochemistry and Plant Systematics, National Research Centre, 33 El Bohouth St., Dokki, Giza 12622, Egypt
Ahmed Mostafa
Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, 33 El Bohouth St., Dokki, Giza 12622, Egypt
Alia Y. Ragheb
Department of Phytochemistry and Plant Systematics, National Research Centre, 33 El Bohouth St., Dokki, Giza 12622, Egypt
Sara H. Mahmoud
Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, 33 El Bohouth St., Dokki, Giza 12622, Egypt
Mahmoud Shehata
Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, 33 El Bohouth St., Dokki, Giza 12622, Egypt
Noura M. Abo Shama
Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, 33 El Bohouth St., Dokki, Giza 12622, Egypt
Mohamed GabAllah
Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, 33 El Bohouth St., Dokki, Giza 12622, Egypt
Gomaa Mostafa-Hedeab
Pharmacology Department & Health Research Unit, Medical College, Jouf University, Skaka 11564, Saudi Arabia
Mona M. Marzouk
Department of Phytochemistry and Plant Systematics, National Research Centre, 33 El Bohouth St., Dokki, Giza 12622, Egypt
Flavonoids are important secondary plant metabolites that have been studied for a long time for their therapeutic potential in inflammatory diseases because of their cytokine-modulatory effects. Five flavonoid aglycones were isolated and identified from the hydrolyzed aqueous methanol extracts of Anastatica hierochuntica L., Citrus reticulata Blanco, and Kickxia aegyptiaca (L.) Nabelek. They were identified as taxifolin (1), pectolinarigenin (2), tangeretin (3), gardenin B (4), and hispidulin (5). These structures were elucidated based on chromatographic and spectral analysis. In this study, molecular docking studies were carried out for the isolated and identified compounds against SARS-CoV-2 main protease (Mpro) compared to the co-crystallized inhibitor of SARS-CoV-2 Mpro (α-ketoamide inhibitor (KI), IC50 = 66.72 µg/mL) as a reference standard. Moreover, in vitro screening against SARS-CoV-2 was evaluated. Compounds 2 and 3 showed the highest virus inhibition with IC50 12.4 and 2.5 µg/mL, respectively. Our findings recommend further advanced in vitro and in vivo studies of the examined isolated flavonoids, especially pectolinarigenin (2), tangeretin (3), and gardenin B (4), either alone or in combination with each other to identify a promising lead to target SARS-CoV-2 effectively. This is the first report of the activity of these compounds against SARS-CoV-2.
