Molecular aspects on Anti-SARS-CoV-2 activity of flavonols: Inhibitory on protein targets, immunomodulatory, and anti-inflammatory effects

Globally, millions of deaths were caused by a novel coronavirus outbreak in December 2019, known as SARS-CoV-2. The main protease (Mpro), Chymotrypsin-Like Protease (3CLpro), Papain-Like Protease (PLpro), Spike protein (S protein), and RNA-dependent RNA polymerase (RdRp) are being targeted in order to identify an appropriate candidate to combat this deadly virus. The majority of developed countries have vaccines on hand to prevent infection; however, medications are necessary to assist in controlling COVID-19. Thus, efforts are initiated to explore natural compounds that possess antiviral properties. Various research findings have shown that flavonoids, especially flavonols and their derivatives, exhibit significant inhibitory effects on viral enzymes and possess antiviral properties. These flavonols neutralize 3CLpro or interfere with gut microbiota in order to maintain immune function. The dual functionality of angiotensin-converting enzyme 2 (ACE2) could potentially play a role in mitigating excessive inflammatory reactions triggered by SARS-CoV-2. Additionally, flavonols can exert immunomodulatory effects by regulating inflammatory mediators, which may prove helpful in controlling cytokine storms associated with SARS-CoV-2 infections. Taking these considerations into account, the present chapter focuses on the flavonol structure and its ability to combat SARS-CoV-2 effects. Furthermore, immunomodulating effects of flavonols and their utility in the management of SARS-COV-2 were also discussed. This chapter will assist in identifying better natural flavonol-based compounds against COVID-19 and synthesizing them as medicinal agents.