Abstract: molecules Review Quercetin: A Functional Food-Flavonoid Incredibly Attenuates Emerging and Re-Emerging Viral Infections through Immunomodulatory Actions Fauzia Mahanaz Shorobi 1 , Fatema Yasmin Nisa 3 , Srabonti Saha 3 , Muhammad Abid Hasan Chowdhury 4 , Mayuna Srisuphanunt 2 , Kazi Helal Hossain 5 and Md. Atiar Rahman 2,3, * 1 2 3 4 5 * Citation: Shorobi, F.M.; Nisa, F.Y.; Saha, S.; Chowdhury, M.A.H.; Srisuphanunt, M.; Hossain, K.H.; Rahman, M.A. Quercetin: A Functional Food-Flavonoid Incredibly Attenuates Emerging and Re-Emerging Viral Infections through Immunomodulatory Actions. Molecules 2023, 28, 938. https://doi.org/10.3390/ molecules28030938 Academic Editor: Jolanta Sereikaitė Received: 11 December 2022 Department of Environmental and Biological Chemistry, Chungbuk National University, Cheongju 28644, Republic of Korea School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand Department of Biochemistry and Molecular Biology, University of Chittagong, Chittagong 4331, Bangladesh Bangladesh Tea Research Institute, Sreemangal-3210, Moulvibazar District, Sylhet 3100, Bangladesh Department of Neuroscience, Lerner Research Institute, Cleveland Clinic, 9620 Carnegie Avenue, Cleveland, OH 44195, USA Correspondence: atiar@cu.ac.bd Abstract: Many of the medicinally active molecules in the flavonoid class of phytochemicals are being researched for their potential antiviral activity against various DNA and RNA viruses. Quercetin is a flavonoid that can be found in a variety of foods, including fruits and vegetables. It has been reported to be effective against a variety of viruses. This review, therefore, deciphered the mechanistic of how Quercetin works against some of the deadliest viruses, such as influenza A, Hepatitis C, Dengue type 2 and Ebola virus, which cause frequent outbreaks worldwide and result in significant morbidity and mortality in humans through epidemics or pandemics. All those have an alarming impact on both human health and the global and national economies. The review extended computing the Quercetin-contained natural recourse and its modes of action in different experimental approaches leading to antiviral actions. The gap in effective treatment emphasizes the necessity of a search for new effective antiviral compounds. Quercetin shows potential antiviral activity and inhibits it by targeting viral infections at multiple stages. The suppression of viral neuraminidase, proteases and DNA/RNA polymerases and the alteration of many viral proteins as well as their immunomodulation are the main molecular mechanisms of Quercetin’s antiviral activities. Nonetheless, the huge potential of Quercetin and its extensive use is inadequately approached as a therapeutic for emerging and re-emerging viral infections. Therefore, this review enumerated the food-functioned Quercetin source, the modes of action of Quercetin for antiviral effects and made insights on the mechanism-based antiviral action of Quercetin. Keywords: quercetin; antiviral action; flavonoid; SARS-CoV-2; Dengue; Ebola; influenza; hepatitis C virus; mechanisms; medicinal plant Revised: 5 January 2023 Accepted: 10 January 2023 Published: 17 January 2023