Anti-COVID-19 Potential of Ellagic Acid and Polyphenols of <i>Punica granatum</i> L.
Ralitza Alexova,
Simona Alexandrova,
Stela Dragomanova,
Reni Kalfin,
Ayten Solak,
Sidharth Mehan,
Maria Cristina Petralia,
Paolo Fagone,
Katia Mangano,
Ferdinando Nicoletti,
Lyubka Tancheva
Affiliations
Ralitza Alexova
Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University—Sofia, Zdrave Str. 2, 1431 Sofia, Bulgaria
Simona Alexandrova
Department of Biological Effects of Natural and Synthetic Substances, Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. Georgi Bonchev Str., Block 23, 1113 Sofia, Bulgaria
Stela Dragomanova
Department of Pharmacology, Toxicology and Pharmacotherapy, Faculty of Pharmacy, Medical University, Marin Drinov Str. 55, 9002 Varna, Bulgaria
Reni Kalfin
Department of Biological Effects of Natural and Synthetic Substances, Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. Georgi Bonchev Str., Block 23, 1113 Sofia, Bulgaria
Ayten Solak
Institute of Cryobiology and Food Technologies, Cherni Vrah Blvd. 5, 1407 Sofia, Bulgaria
Sidharth Mehan
Department of Pharmacology, Division of Neuroscience, ISF College of Pharmacy, Moga 142001, India
Maria Cristina Petralia
Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy
Paolo Fagone
Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 89, 95123 Catania, Italy
Katia Mangano
Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 89, 95123 Catania, Italy
Ferdinando Nicoletti
Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 89, 95123 Catania, Italy
Lyubka Tancheva
Department of Biological Effects of Natural and Synthetic Substances, Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. Georgi Bonchev Str., Block 23, 1113 Sofia, Bulgaria
Pomegranate (Punica granatum L.) is a rich source of polyphenols, including ellagitannins and ellagic acid. The plant is used in traditional medicine, and its purified components can provide anti-inflammatory and antioxidant activity and support of host defenses during viral infection and recovery from disease. Current data show that pomegranate polyphenol extract and its ellagitannin components and metabolites exert their beneficial effects by controlling immune cell infiltration, regulating the cytokine secretion and reactive oxygen and nitrogen species production, and by modulating the activity of the NFκB pathway. In vitro, pomegranate extracts and ellagitannins interact with and inhibit the infectivity of a range of viruses, including SARS-CoV-2. In silico docking studies show that ellagitannins bind to several SARS-CoV-2 and human proteins, including a number of proteases. This warrants further exploration of polyphenol–viral and polyphenol–host interactions in in vitro and in vivo studies. Pomegranate extracts, ellagitannins and ellagic acid are promising agents to target the SARS-CoV-2 virus and to restrict the host inflammatory response to viral infections, as well as to supplement the depleted host antioxidant levels during the stage of recovery from COVID-19.
