Coronaviruses   11 Furqan Shafqat 1,# , Shafeeq Ur Rehman 1,# , Omazia Nasir 1 , Ayesha Sarwar 2 and Kamal Niaz 3,* 1 Department of Microbiology, Faculty of Veterinary Science, Cholistan University of Veterinary & Animal Sciences, Bahawalpur-63100, Pakistan; 2 Department of Zoology, Wildlife and Fisheries, Faculty of Bio-Sciences, University of Agriculture Faisalabad, Faisalabad, Pakistan; 3 Department of Pharmacology & Toxicology, Faculty of Bio-Sciences, Cholistan University of Veterinary & Animal Sciences, Bahawalpur-63100, Pakistan Abstract: Fruit, vegetables, and green tea contain quercetin (a flavonoid). Some of the diet's most signifi- cant sources of quercetin are apples, onions, tomatoes, broccoli, and green tea. Antioxidant, anticancer, anti-inflammatory, antimicrobial, antibacterial, and anti-viral effects have been studied of quercetin. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus, ribonucleic acid (RNA) polymer- ase, and other essential viral life-cycle enzymes are all prevented from entering the body by quercetin. Despite extensive in vitro and in vivo investigations on the immune-modulating effects of quercetin and vitamin C treatment. 3-methyl-quercetin has been shown to bind to essential proteins necessary to convert minus-strand RNA into positive-strand RNAs, preventing the replication of viral RNA in the cytoplasm. Quercetin has been identified as a potential SARS-CoV-2 3C-like protease (3CL pro ) suppressor in recent molecular docking studies and in silico assessment of herbal medicines. It has been demonstrated that quercetin increases the expression of heme oxygenase-1 through the nuclear factor erythroid-related fac- tor 2 (Nrf2) signal network. Inhibition of heme oxygenase-1 may increase bilirubin synthesis, an endoge- nous antioxidant that defends cells. When human gingival fibroblast (HGF) cells were exposed to lipo- polysaccharide (LPS), inflammatory cytokine production was inhibited. The magnesium (Mg +2 ) cation complexation improves quercetin free radical scavenging capacity, preventing oxidant loss and cell death. The main objective of this paper is to provide an overview of the pharmacological effects of quercetin, its protective role against SARS-CoV-2 infection, and any potential molecular processes. A R T I C L E H I S T O R Y Received: July 15, 2022 Revised: October 27, 2022 Accepted: November 01, 2022 DOI: 10.2174/2666796704666221123105201 Keywords: Quercetin, SARS-CoV-2, antioxidant, biological, protease, analysis. 1. INTRODUCTION Quercetin (3,3′,4′,5,7-pentahydroxyfavone) is a flavonoid molecule in various foods, including vegetables and fruits. Apples, lettuce, tomatoes, onions, broccoli, and black and green tea are some of the best suppliers of quercetin in the diet. Antimicrobial, antibacterial, anti-inflammatory, anti- cancer, and antioxidant actions have been documented for quercetin [1], as shown in Fig. (1). One potential reason is that quercetin glycosides are hydrolyzed as they are changed to aglycone by β-glycosidase enzymes. Quercetin is mostly found in food linked with sugars, phenolic acids, alcohols, and other compounds. Following intake, quercetin byprod- ucts are mainly analyzed in the gastrointestinal system be- fore being absorbed and metabolized. Quercetin also operat- ed as a free radical scavenger, providing reduced oxidized *Address correspondence to this author at the Department of Pharmacology & Toxicology, Faculty of Bio-Sciences, Cholistan University of Veterinary & Animal Sciences, Bahawalpur-63100, Pakistan; Tel: +923129360054; E-mails: kamalniaz@cuvas.edu.pk; kamalniaz1989@gmail.com # These authors contributed equally to this work. molecules with two electrons. When this occurs, with one electron being moved simultaneously, a semiquinone precur- sor molecule is formed. Ascorbate can recover the flavanol molecule, protect it from oxidation, and restore the oxidized quinolinic form after scavenging free radicals. Quercetin antioxidant ability may operate in tandem with vitamin C. Research on the potential anti-viral properties of querce- tin has focused on many members of the Coronaviridae family. Quercetin "provides tremendous promise as a poten- tial drug in the therapeutic practice of SARS," as Ling Yi and coworkers put it [2]. SARS-CoV was primarily reported in 2003 as a single-stranded ribonucleic acid (RNA) virus of 29,700 nucleotides in length. It produces two replicase gly- coproteins, polyproteins 1a and 1b (pp1a and pp1b), at ribo- some sites to aid in viral replication [3, 4]. A 3C-like prote- ase (3CL pro ) is essential for the lytic release of the duplicates of these precursor glycoproteins after they have been pro- duced [5]. With an IC 50 value of 42.79 ± 4.95 M, quercetin- 3b-galactoside binds to the SARS-CoV antagonist 3CL pro [6]. According to molecular modeling and the Q189A muta- tion, quercetin's hydroxyl group causes this antagonistic ef- fect on 3CL pro , identifying Gln189 as a critical location on Send Orders for Reprints to reprints@benthamscience.net Coronaviruses, 2022, 3, e231122211149 REVIEW ARTICLE Landscape Analysis of Quercetin: A Potential Candidate Against SARS- CoV-2 2666-7975/22 $65.00+.00 © 2022 Bentham Science Publishers