4.21. Poly-Alcohols: Resveratrol and Quercetin
On the one hand, resveratrol is a natural polyphenolic stilbene derivative (Figure 9). Resveratrol exhibits several biological activities, including antioxidant, antitumor, anti-inflammatory, oxygen scavenging, and antiviral activities. Resveratrol inhibits TNF-induced activation of NF-κB in a dose-dependent manner. Furthermore, it inhibits cyclooxygenase and hydro-peroxidase enzymes. Not only that but it also inhibits vascular cell adhesion molecule expression and vascular smooth muscle cell proliferation. It also stimulates endothelial nitric oxide synthase activity and inhibits platelet aggregation and LDL peroxidation [276,277,278]. All these effects are expected to help fight COVID-19 infection and its complications. Importantly, resveratrol significantly inhibited MERS-CoV replication in vitro mainly by inhibiting the RNA production [279]. Resveratrol also inhibited the replication of duck enteritis virus [280] and pseudorabies virus [281]. Accordingly, the safety and efficacy of resveratrol in COVID-19 patients are being tested in a randomized double-blind, placebo-controlled proof-of-concept trial (NCT04400890; n = 200).
On the other hand, quercetin is a natural penta-hydroxylated flavonoid (Figure 9). Similar to resveratrol, quercetin possesses antioxidant, oxygen scavenging, anti-inflammatory, and cardioprotective effects. Quercetin also inhibits platelet aggregation and lipid peroxidation and affects the function of several kinases [282]. Importantly, quercetin also exhibits a wide spectrum antiviral activity against DNA and RNA viruses. For example, quercetin inhibited several respiratory viruses in cultured cells. It also inhibited the cytopathic effects of rhinoviruses, echoviruses, coxsackieviruses, and polioviruses [283,284,285]. Quercetin also significantly reduced plaque formation by polio virus, herpes simplex virus 1, respiratory syncytial virus, and parainfluenza virus [286]. Furthermore, quercetin inhibited the replication of cytomegalovirus and dengue virus 2 [287]. The antiviral effects of quercetin are thought to be because it either blocks the virus entry or inhibits the viral replication enzymes, i.e., viral polymerases [288]. Other flavonoids have recently been reported as potential inhibitors of Mpro [289]. Accordingly, the effect of quercetin alone as a prophylactic or as a treatment is being tested in COVID-19 patients (NCT04377789; 50). It is also being tested with zinc, bromelain, and vitamin C (NCT04468139; n = 60).