Quercetin, a naturally occurring dietary flavonoid, is well known to ameliorate chronic diseases and aging processes in humans, and its antiviral properties have been investigated in numerous studies. In silico and in vitro studies demonstrated that quercetin can interfere with various stages of the coronavirus entry and replication cycle such as PLpro, 3CLpro, and NTPase/helicase. Due to its pleiotropic activities and lack of systemic toxicity, quercetin and its derivatives may represent target compounds to be tested in future clinical trials to enrich the drug arsenal against coronavirus infections. There is evidence that quercetin in combination with, for example, vitamins C and D, may exert a synergistic antiviral action that may provide either an alternative or additional therapeutic/preventive option due to overlapping antiviral and immunomodulatory properties. This review summarizes the antiviral significance of quercetin and proposes a possible strategy for the effective utilization of natural polyphenols in our daily diet for the prevention of viral infection.

Various computational studies, including in silico ones, have identified several existing compounds that could serve as effective inhibitors of the SARS-CoV-2 main protease (M^pro), and thus preventing replication of the virus. Among these, rutin has been identified as a potential hit, having prominent binding affinity to the virus. Moreover, its presence in several traditional antiviral medicines prescribed in China to infected patients with mild to moderate symptoms of COVID-19 justify its promise as a repurposed bioactive secondary metabolite against SARS-CoV-2.

Hesperidin and hesperetin are flavonoids that are abundantly present as constituents of citrus fruits. These compounds have attracted attention as several computational methods, mostly docking studies, have shown that hesperidin may bind to multiple regions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (spike protein, angiotensin-converting enzyme 2, and proteases). Hesperidin has a low binding energy, both with the SARS-CoV-2 “spike” protein responsible for internalization, and also with the “PL^pro” and “M^pro” responsible for transforming the early proteins of the virus into the complex responsible for viral replication. This suggests that these flavonoids could act as prophylactic agents by blocking several mechanisms of viral infection and replication, and thus helping the host cell to resist viral attack.

As the world desperately searches for ways to treat the coronavirus disease 2019 (COVID-19) pandemic, a growing number of people are turning to herbal remedies. The Artemisia species, such as A. annua and A. afra, in particular, exhibit positive effects against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and COVID-19 related symptoms. A. annua is a source of artemisinin, which is active against malaria, and also exhibits potential for other diseases. This has increased interest in artemisinin’s potential for drug repurposing. Artemisinin-based combination therapies, so-called ACTs, have already been recognized as first-line treatments against malaria. Artemisia extract, as well as ACTs, have demonstrated inhibition of SARS-CoV-2. Artemisinin and its derivatives have also shown anti-inflammatory effects, including inhibition of interleukin-6 (IL-6) that plays a key role in the development of severe COVID-19. There is now sufficient evidence in the literature to suggest the effectiveness of Artemisia, its constituents and/or artemisinin derivatives, to fight against the SARS-CoV-2 infection by inhibiting its invasion, and replication, as well as reducing oxidative stress and inflammation, and mitigating lung damage.

Naringenin, widely distributed in fruits and vegetables, is endowed with antiviral and other health beneficial activities, such as immune-stimulating and anti-inflammatory actions that could play a role in contributing, to some extent, to either preventing or alleviating coronavirus infection. Several computational studies have identified naringenin as one of the prominent flavonoids that can possibly inhibit internalization of the virus, virus-host interactions that trigger the cytokine storm, and replication of the virus. This review highlights the antiviral potential of naringenin in COVID-19 associated risk factors and its predicted therapeutic targets against SARS-CoV-2 infection.

Myricetin (3,5,7,3′,4′,5′ -hexahydroxyflavone), a common dietary flavonoid, has been reported for its roles in improving health due to various pharmacological activities, such as antioxidant, antimicrobial, anti-inflammatory, analgesic, antitumor, hepatoprotective, and antidiabetic. Myricetin has also been shown to have a broad spectrum of antiviral effects against a variety of viruses including Rauscher murine leukemia virus (RLV), human immunodeficiency virus (HIV), Coxsackie virus, Ebolavirus, Zika virus, herpes simplex virus (HSV-1 and HSV-2), dengue virus, murine norovirus, infectious bronchitis virus, African swine fever virus, and both DNA polymerase α and DNA polymerase I. Intensive research suggests that the remarkable potential of myricetin in promoting either the prevention or overcoming of SARS-CoV-2 infection is due to the wide range of its effects on SARS-COV-2 proteases, including modulation of inflammatory processes and immune responses. In silico and in vitro studies demonstrated that myricetin can effectively interfere at various stages of viral infection, including the coronavirus entry and replication cycle due to its high-binding affinity with S-protein, ACE2 receptor, PLpro, Mpro, RdRp, exonuclease, and endoribonuclease. Based on the findings discussed in this review, myricetin, its glycosides, and dihydromyricetin, can be considered as multi-targeted agents having beneficial effects in combatting COVID-19.