Quercetin: A Functional Food-Flavonoid Incredibly Attenuates Emerging and Re-Emerging Viral Infections through Immunomodulatory Actions

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: Dengue; Ebola; SARS-CoV-2; antiviral action; flavonoid; hepatitis C virus; influenza; mechanisms; medicinal plant; quercetin.

Figure 1

Chemical illustration of Quercetin taken from pubChem.

Figure 2

Schematic design aiming the approach and objective of this review.

Figure 3

Effects of Quercetin in reducing the membrane area of Hepatitis C virus. The Hepatitis C virus entered the cellular system and is finally weakened through the protein molecule Diglyceride acyltransferase (DGAT, subtype DGAT1), which is inhibited by the administration of Quercetin. Inhibited DGAT downregulates the lipid synthesis, HCV core protein is eventually neutralized through the reduction of lipid droplets (LDs) size, which decreases the membrane size for HCV. HCV infections become attenuated.

Figure 4

Effects of Quercetin in redirecting the virulence-mechanism of dengue virus. Ejection of Dengue virus particles from the cellular system with the involvement of cascade molecules, such as JAK, KFKB, STAT 1, STAT 2, NS2A, NS2B, SOCS, and SHP. The mechanism is assisted by the direct effect of Quercetin on the inhibition of the NF-kB pathway, which induces the production of a number of inflammatory and proinflammatory molecules. Interferon regulatory factors IFN, IRF3, and IRF7 are concomitantly reduced. The indirect effect of Quercetin is mediated by the inhibitory cascade of tumor necrosis factor, which affects the synthesis of IL6 and eventually leads to the restoration of Janus kinase (JAK)-signal transducer and activator of the transcription (STAT) pathway.

Figure 5

Effects of Quercetin on the Influenza virus. Quercetin augments in destructing the viral polymerase while its major target is viral RNA. Quercetin targets hemagglutinin (HA), which is a major determinant in subtype specificity. Subsequently the packaging subunit of viral RNA polymerase (PB1, PB2), acidic RNA polymerase (PA), nucleoprotein (NP), matrix protein (M1 and M2) and nonstructural protein (NS1 and NS2) subtypes of viral polymerase finally attenuate the RNA polymerase of Influenza virus through the removal of PB2, PA, NP and M segments.

Figure 6

The unenveloped genetic material of the Ebola virus has interacted with Quercetin and with the aid of interferon-sensitive response element (ISRE) expression, ISG15 mRNA transcription, and phosphorylated STAT1 (P-STAT1) nuclear transport, replication of the Ebola virus approach to be halted. EBOV nucleocapsid proteins—nucleoprotein (NP), viral protein (VP35, VP24, VP30, VP40), and glycoprotein (GP) while NP, VP2,4 and VP 35 are necessary and sufficient to form transport-competent nucleocapsid-like structures. Quercetin directly restores the VP24 which is blocked by the Ebola virus and indirectly by using ISRE, ISG15 and STAT1.

Figure 7

Immunomodulatory highlights on different antiviral mechanisms of action of Quercetin and its derivates. (A) Quercetin blocks virus entry or virus replication through interaction with viral proteins. (B) Immunomodulatory factors interleukins, tumor necrosis factor, and nonstructural viral proteins regulated by Quercetin play a key role in protecting the viral infections.

Figure 8

Differences in the mechanism of action of Quercetin for inhibiting four different types of viruses. The viral strains are denoted as hepatitis C virus (HCV), Dengue virus (DENV), Ebola virus (EBOV), and Influenzae virus (IAV).