The Therapeutic and Prophylactic Potential of Quercetin against COVID-19: An Outlook on the Clinical Studies, Inventive Compositions, and Patent Literature
Mohd Imran, Hamdy Khamees Thabet, Saleh I Alaqel, Abdullah R Alzahrani, Abida Abida, Mohammed Kanan Alshammari, Mehnaz Kamal, Anupama Diwan, Syed Mohammed Basheeruddin Asdaq, Sultan Alshehri
Antioxidants, doi:10.3390/antiox11050876
Quercetin is a phenolic flavonol compound with established antioxidant, anti-inflammatory, and immuno-stimulant properties. Recent studies demonstrate the potential of quercetin against COVID-19. This article highlighted the prophylactic/therapeutic potential of quercetin against COVID-19 in view of its clinical studies, inventions, and patents. The literature for the subject matter was collected utilizing different databases, including PubMed, Sci-Finder, Espacenet, Patentscope, and USPTO. Clinical studies expose the potential of quercetin monotherapy, and also its combination therapy with other compounds, including zinc, vitamin C, curcumin, vitamin D3, masitinib, hydroxychloroquine, azithromycin, and ivermectin. The patent literature also examines claims that quercetin containing nutraceuticals, pharmaceuticals, and dietary supplements, alone or in combination with other drugs/compounds, including favipiravir, remdesivir, molnupiravir, navitoclax, dasatinib, disulfiram, rucaparib, tamarixin, iota-carrageenan, and various herbal extracts (aloe, poria, rosemary, and sphagnum) has potential for use against COVID-19. The literature reveals that quercetin exhibits anti-COVID-19 activity because of its inhibitory effect on the expression of the human ACE2 receptors and the enzymes of SARS-CoV-2 (MPro, PLPro, and RdRp). The USFDA designated quercetin as a "Generally Recognized as Safe" substance for use in the food and beverage industries. It is also an inexpensive and readily available compound. These facts increase the possibility and foreseeability of making novel and economical drug combinations containing quercetin to prevent/treat COVID-19. Quercetin is an acidic compound and shows metabolic interaction with some antivirals, antibiotics, and anti-inflammatory agents. Therefore, the physicochemical and metabolic drug interactions between quercetin and the combined drugs/compounds must be better understood before developing new compositions.
Conflicts of Interest: The authors declare no conflict of interest.
References
Adnot, Trottein, Bernard, Method to Treat a Pathogen Lung Infection, PCT Patent Application Publication
Alshrari, Hudu, Imran, Asdaq, Ali et al., Innovations and development of COVID-19 vaccines: A patent review, J. Infect. Public Health,
doi:10.1016/j.jiph.2021.10.021Ansari, Abdul, Joshi, Opii, Butterfield, Protective effect of quercetin in primary neurons against Abeta(1-42): Relevance to Alzheimer's disease, J. Nutr. Biochem,
doi:10.1016/j.jnutbio.2008.03.002Asdaq, Rabbani, Alkahtani, Aldohyan, Alabdulsalam et al., A Patent Review on the Therapeutic Application of Monoclonal Antibodies in COVID-19, Int. J. Mol. Sci,
doi:10.3390/ijms222111953Aucoin, Cooley, Saunders, Cardozo, Remy et al., The effect of quercetin on the prevention or treatment of COVID-19 and other respiratory tract infections in humans: A rapid review, Adv. Integr. Med,
doi:10.1016/j.aimed.2020.07.007Barnhill, Antiviral Compositions and Methods for Their Use, PCT Patent Application Publication
Bernini, Velotti, Natural Polyphenols as Immunomodulators to Rescue Immune Response Homeostasis: Quercetin as a Research Model against Severe COVID-19, Molecules,
doi:10.3390/molecules26195803Bhat, Bhat, Quercetin: A Bioactive Compound Imparting Cardiovascular and Neuroprotective Benefits: Scope for Exploring Fresh Produce, Their Wastes, and By-Products, Biology,
doi:10.3390/biology10070586Biancatelli, Berrill, Catravas, Marik, Quercetin, Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19), Front. Immunol,
doi:10.3389/fimmu.2020.01451Budak, Budak, The Natural Antiviral and Anti-Inflammatory Compound Consist of Bioflavonoids Which Extracted from Papaver Rhoeas Red Petals, PCT Patent Application Publication
Chung, Lee, Kim, Lee, Lee, Coronavirus Therapeutic Agent Comprising Zanthoxylum piperitum Leaf Extract as Active Ingredient, PCT Patent Application Publication
Costela-Ruiz, Illescas-Montes, Puerta-Puerta, Ruiz, Melguizo-Rodríguez, SARS-CoV-2 infection: The role of cytokines in COVID-19 disease, Cytokine Growth Factor Rev,
doi:10.1016/j.cytogfr.2020.06.001Dabbagh-Bazarbachi, Clergeaud, Quesada, Ortiz, O'sullivan et al., Zinc ionophore activity of quercetin and epigallocatechin-gallate: From Hepa 1-6 cells to a liposome model, J. Agric. Food. Chem
David, Arulmoli, Parasuraman, Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid, Pharmacogn. Rev
Davidoff, Methods of Treating Viral Infections and Health Consequences, PCT Patent Application Publication
Derosa, Maffioli, D'angelo, Di Pierro, A role for quercetin in coronavirus disease 2019 (COVID-19), Phytother. Res,
doi:10.1002/ptr.6887Di Pierro, Derosa, Maffioli, Bertuccioli, Togni et al., Possible Therapeutic Effects of Adjuvant Quercetin Supplementation Against Early-Stage COVID-19 Infection: A Prospective, Randomized, Controlled, and Open-Label Study, Int. J. Gen. Med,
doi:10.2147/IJGM.S318720Di Pierro, Iqtadar, Khan, Ullah Mumtaz, Masud Chaudhry et al., Potential Clinical Benefits of Quercetin in the Early Stage of COVID-19: Results of a Second, Pilot, Randomized, Controlled and Open-Label Clinical Trial, Int. J. Gen. Med,
doi:10.2147/IJGM.S318949Di Pierro, Khan, Bertuccioli, Maffioli, Derosa et al., Quercetin Phytosome®as a potential candidate for managing COVID-19, Minerva Gastroenterol. Torino,
doi:10.23736/S2724-5985.20.02771-3Diniz, Souza, Duarte, Sousa, Mechanistic Aspects and Therapeutic Potential of Quercetin against COVID-19-Associated Acute Kidney Injury, Molecules,
doi:10.3390/molecules25235772Dite, Murphy, Allman, Methods of Assessing Risk of Developing a Severe Response to Coronavirus Infection, PCT Patent Application Publication
Feng, Xu, Gao, Ge, Lu et al., Application of Quercetin to Preparation of Anti-Novel Coronavirus Drugs, Chinese Patent Application Publication
Feng, Zhu, Liu, Liu, Zhou et al., Yindan Jiedu granules exhibit anti-inflammatory effect in patients with novel Coronavirus disease (COVID-19) by suppressing the NF-κB signaling pathway, Phytomedicine,
doi:10.1016/j.phymed.2021.153784Finzi, Zinc for Treating COVID-19, PCT Patent Application Publication Number
Fliri, Drug Combinations for Inhibiting Infectivity of Influenza and Corona Viruses, PCT Patent Application Publication
Ghaderi, Compositions and Methods for Inducing Biological Mimicry in a Mammal for the Prevention and/or Treatment of COVID-19 and Other Diseases, U.S. Patent Application No
Hahn, Nutraceutical Composition, PCT Patent Application Publication
Hashemian, Farhadi, Velayati, A review on favipiravir: The properties, function, and usefulness to treat COVID-19, Expert Rev. Anti. Infect. Ther,
doi:10.1080/14787210.2021.1866545Hazan, Methods of Preventing and Treating COVID-19 Infection, U.S. Patent Application No
Hickok, Improved Immunomodulator Compositions and Viral Pathogen Treatments, PCT Patent Application Publication
Hoag, Salerno, Method for Treating Viral and Bacterial Infection Through Inhalation Therapy, PCT Patent Application Publication
Hofleitner, Composition for Treating Viral Infections, PCT Patent Application Publication
Ichim, Lin, Pingle, Ashili, Augmentation of Cell Therapy Efficacy by Inhibition of Complement Activation Pathways, U.S. Patent Application No
Ichim, Lin, Pingle, Ashili, Treatment of Acute Respiratory Distress Syndrome by T Regulatory Cells, U.S. Patent Application No
Ichim, O'heeron, Fibroblast Mediated Expansion and Augmentation of Immune Regulatory Cells for Treatment of Acute Respiratory Distress Syndrome (ARDS), PCT Patent Application Publication
Imran, Alsharari, Thabet, Abida, None
Imran, Alshrari, Asdaq, Abida, Trends in the development of remdesivir based inventions against COVID-19 and other disorders: A patent review, J. Infect. Public Health,
doi:10.1016/j.jiph.2021.06.013Imran, Asdaq, Khan, Unnikrishnan Meenakshi, Alamri et al., Innovations and Patent Trends in the Development of USFDA Approved Protein Kinase Inhibitors in the Last Two Decades, Pharmaceuticals,
doi:10.3390/ph14080710Imran, Khan, Abida' Alshrari, Eltahir Mudawi, Alshammari et al., Small molecules as kinetoplastid specific proteasome inhibitors for Leishmaniasis: A patent review from 1998 to 2021, Expert Opin. Ther. Pat,
doi:10.1080/13543776.2022.2045948Imran, Khan, Alshammari, Alqahtani, Alanazi et al., Development, Inventions and Patent Review of Fexinidazole: The First All-Oral Therapy for Human African Trypanosomiasis, Pharmaceuticals,
doi:10.3390/ph15020128Imran, Khan, Alshammari, Alreshidi, Alreshidi et al., Development, Inventions, and Patent Trends on Mobocertinib Succinate: The First-in-Class Oral Treatment for NSCLC with EGFR Exon 20 Insertions, Biomedicines,
doi:10.3390/biomedicines9121938Imran, Kumar, Asdaq, Khan, Alaqel et al., Discovery, Development, and Patent Trends on Molnupiravir: A Prospective Oral Treatment for COVID-19, Molecules,
doi:10.3390/molecules26195795Jain, Method and System for Detecting and Treating Exposure to an Infectious Pathogen, PCT Patent Application Publication
Kang, Kwon, Jung, Choi, Lee, SARS-CoV-2 Composition for the Prevention or Treatment of SARS-CoV-2 Infection Comprising the Extract of Agrimonia pilosa as an Active Ingredient, Korean Patent Application Publication
Kelesidis, Arumugaswami, Garcia, Compositions and Methods for Inhibiting and Treating Coronavirus Infections, PCT Patent Application Publication
Khalil, El-Latif, A New and Safe Pharmaceutical Preparation for Prophylaxis and Treatment of Respiratory Viral Infections, Especially Corona Viruses, PCT Patent Application Publication
Kumar, Rai, Khan, Kumar, Haque et al., Role of herbal medicines in the management of patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials, J. Tradit. Complement. Med,
doi:10.1016/j.jtcme.2022.01.002Lane, Hunter, Lee, Hyman, Bross et al., Clinical characteristics and symptom duration among outpatients with COVID-19, Am. J. Infect. Control,
doi:10.1016/j.ajic.2021.10.039Lecanu, Pannexin-1 Inhibitors for the Treatment of SARS-COV-2 Infected COVID-19 Patients with or without an Associated Acute Respiratory Syndrome, PCT Patent Application Publication
Li, Miao, Zhao, Xu, Pan et al., Small-Molecule Inhibitor for Blocking Combination of COVID-19 Spinous Protein and Human Angiotensin Converting Enzyme 2 and Application Thereof, Chinese Patent Application Publication
Manjunath, Thimmulappa, Antiviral, immunomodulatory, and anticoagulant effects of quercetin and its derivatives: Potential role in prevention and management of COVID-19, J. Pharm. Anal,
doi:10.1016/j.jpha.2021.09.009Margolin, Compositions and Methods for Dietary Enhancement of Immune System Function, U.S. Patent Application No
Margolin, Luchins, Margolin, Margolin, Lefkowitz, 20-Week Study of Clinical Outcomes of Over-the-Counter COVID-19 Prophylaxis and Treatment, J. Evid. Based Integr Med,
doi:10.1177/2515690X211026193Markoulaki, Iordanou, Koukios, Christoldoulou, Papadopoulos et al., Severe Multisystem Inflammatory Syndrome Associated with SARS-CoV-2 in a 31-Year-Old Male Patient: The First Clinical Case Report from the Republic of Cyprus, Cureus,
doi:10.7759/cureus.22640Mcmahon, Watson, Viral Treatments Involving Manuka Honey and Components Thereof, PCT Patent Application Publication
Meydani, Mozaffarian, Nutritional Supplement to Combat COVID-19 and Aid Vaccination, U.S. Patent Application No
Newman, Addington, Method and Compositions for Treating Coronavirus Infection, U.S. Patent
Newman, Addington, Obiso, Method and Compositions for Treating Coronavirus Infection, PCT Patent Application Publication
Newman, Addington, Obiso, Method and Compositions for Treating Coronavirus Infection, PCT Patent Application Publication
Nezami, Compositions and Methods for Preventing and/or Treating Viral Infection, PCT Patent Application Publication
Niedzwiecki, Rath, Ivanov, Goc, Micronutrient Combination to Inhibit Coronavirus Cell Infection, U.S. Patent Application No
Niedzwiecki, Rath, Ivanov, Goc, Pharmaceutical Micronutrient Composition, and Its Use to Simultaneously Inhibit Multiple Cellular Mechanisms of Infectivity Caused by Coronavirus, Its Variants and Mutants, U.S. Patent Application No
O'heeron, Ichim, Reduction of Cytokine Storm and Pathological Inflammation Including Caused by Coronavirus Using Sphagnum and Extracts Thereof, PCT Patent Application Publication
Obiso, Newman, Addington, Extract Containing Oleandrin and Method of Production Thereof, PCT Patent Application Publication
Parkin, Wells, Dransfield, Methods Involving Neutrophil Elastase Inhibitor Alvelestat for Treating Coronavirus Infection, PCT Patent Application Publication
Popov, Josling, Compositions and Applications Thereof, PCT Patent Application Publication
Rincome, Rincome, Fermented-Concentrated Extraction Method of Houttuynia cordata for Medical Using, PCT Patent Application Publication
Robitaille, Laurin, Gagnon, Cesari, Pharmacotherapeutic Doses of Hesperidin or Related Bioflavonoids to Adress Infectious and/or Inflammatory Diseases, PCT Patent Application Publication
Rondanelli, Perna, Gasparri, Petrangolini, Allegrini et al., Promising Effects of 3-Month Period of Quercetin Phytosome®Supplementation in the Prevention of Symptomatic COVID-19 Disease in Healthcare Workers: A Pilot Study, Life,
doi:10.3390/life12010066Salunke, Salunke, Patil, A Composition for Management of COVID-19 and Associated Disorders, PCT Patent Application Publication
Schack, Campbell, Anthocyanin and Quercetin Based Formulations for Improved Respiratory Health, U.S. Patent Application No
Shohan, Nashibi, Mahmoudian-Sani, Abolnezhadian, Ghafourian et al., The therapeutic efficacy of quercetin in combination with antiviral drugs in hospitalized COVID-19 patients: A randomized controlled trial, Eur. J. Pharmacol,
doi:10.1016/j.ejphar.2021.174615Spadavecchia, Giousuè Balzanelli, Derrien, Composition for the Prevention or Treatment of COVID-19, PCT Patent Application Publication
St, John, Targeting Immune Pathologies Induced by Highly Pathogenic Coronaviruses, PCT Patent Application Publication
Stafford, Method to Mitigate Morbidity and Mortality in Virally Induced forms of ACE2 Receptor Pathology Progressing to SARS or ARDS, U.S. Patent Application No
Su, Yang, Zhong, Ma, Li et al., Herba Hyperici Japonici Extract and Application Thereof in Preparation of Novel Coronavirus Resistant Drug, Chinese Patent Application Publication
Suzman, Fisherman, Lunsmann, Methods and Compositions for Treating Viral Respiratory Infections, PCT Patent Application Publication No
Vecht-Lifshitz, Pharmaceutical Compositions for Treating Corona Virus Disease, PCT Patent Application Publication Number
Vishwakarma, Panigrahi, Barua, Sahoo, Mandliya, Food nutrients as inherent sources of immunomodulation during COVID-19 pandemic, Lebensm. Wiss. Technol,
doi:10.1016/j.lwt.2022.113154Voelkel, Magolske, Method and Composition for Treating Coronavirus, Influenza, and Acute Respiratory Distress Syndrome, U.S. Patent Application No
Weiguang, Vinodh, Topical Disulfiram for Treating Viral Infections, PCT Patent Application Publication
Winchester, Methods of Diagnosing Risk of Serious Symptoms from COVID-19 Infection, U.S. Patent Application No
Xia, Shi, Su, Friedemann, Tao et al., Shufeng Jiedu, a promising herbal therapy for moderate COVID-19: Antiviral and anti-inflammatory properties, pathways of bioactive compounds, and a clinical real-world pragmatic study, Phytomedicine,
doi:10.1016/j.phymed.2020.153390Xiao, Xiao, Peng, He, Formulations Comprising Botanical Extracts, Australian Patent Application Publication
Yang, Wang, Long, Li, Quercetin: Its Main Pharmacological Activity and Potential Application in Clinical Medicine, Oxid. Med. Cell Longev,
doi:10.1155/2020/8825387Yang, Zhao, Zhang, Zhang, Li, COVID-19 in Elderly Adults: Clinical Features, Molecular Mechanisms, and Proposed Strategies, Aging Dis,
doi:10.14336/AD.2020.0903Ye, Lu, Zhou, Lin, Li et al., Medicinal and Edible Traditional Chinese Medicine Preparation and Application Thereof, Chinese Patent Application Publication
Yimam, Jiao, Horm, Brownell, Hong et al., Aloe Based Compositions Comprising Polysaccharides and Polyphenols for Regulation of Homeostasis of Immunity, U.S. Patent Application No
Zhang, Compositions and Methods for Preventing and/or Treating Microbial Infections, PCT Patent Application Publication
Önal, Arslan, Üçüncü Ergun, Topuz, Yilmaz Semerci et al., Treatment of COVID-19 patients with quercetin: A prospective, single center, randomized, controlled trial, Turk. J. Biol,
doi:10.3906/biy-2104-16
