May Polyphenols Have a Role Against Coronavirus Infection? An Overview of in vitro Evidence

Abstract

The coronavirus infection is constantly diffusing worldwide and the incidence of death is dramatically increasing, representing one of the greatest disasters in human history. Nowadays, no effective therapeutic approaches have been licensed, despite the rising interest of the scientific research in this specific field, and the daily growing number of publications, while the need to find novel strategies is urgent. Evidence in the literature reported the antiviral activity of polyphenols, the largest class of bioactive compounds in nature. Interestingly, a limited number of studies investigated the efficacy of polyphenols from different raw materials, directly against coronaviruses. The present manuscript aimed to report this evidence and provide a viewpoint on the possibility to use it as a start point for the development of novel natural approaches against this viral infection, eventually designing further appropriate researches.

Plants Metabolites: Possibility of Natural Therapeutics Against the COVID-19 Pandemic

“…First and foremost are polyphenols, which contain multiple phenolic rings, and are classified as phenols, flavonoids, lignans, hydroxycinnamic acid, stilbenes, and hydroxybenzoic acid ( 267 ). We found polyphenols in numerous plants ( Table 4 ) which exerted antiviral activity ( 269 – 271 ) against a wide range of viruses including HIV-1, HIV-2, HSV-1, HSV-2, Influenza virus, Dengue virus, HBV, HCV, Infectious bronchitis virus (IBV), Murbarg virus, Ebola virus, Newcastle disease virus (NDV), Poliomyelitis-1 virus, Lentivirus, and Coronavirus. Polyphenols work against coronaviruses using diverse mechanisms including actuating or inhibiting cellular signaling pathways or halting papain-like protease (PL pro ) and 3-chymotripsin-like protease (3CL pro ) enzyme ( 269 , 272 ).…”

“…We found polyphenols in numerous plants ( Table 4 ) which exerted antiviral activity ( 269 – 271 ) against a wide range of viruses including HIV-1, HIV-2, HSV-1, HSV-2, Influenza virus, Dengue virus, HBV, HCV, Infectious bronchitis virus (IBV), Murbarg virus, Ebola virus, Newcastle disease virus (NDV), Poliomyelitis-1 virus, Lentivirus, and Coronavirus. Polyphenols work against coronaviruses using diverse mechanisms including actuating or inhibiting cellular signaling pathways or halting papain-like protease (PL pro ) and 3-chymotripsin-like protease (3CL pro ) enzyme ( 269 , 272 ). Some polyphenol compounds (30-(3-methylbut-2-enyl)-30, 4-hydroxyisolonchocarpin, broussochalcone A, 4,7-trihydroxyflavane, broussochalcone B, papyriflavonol A, kazinol A, kazinol B, kazinol F, kazinol J, and broussoflavan A) isolated from Broussonetia papyrifera showed promising activity against SARS CoV.…”

Mediterranean diet as a nutritional approach for COVID-19

“…In particular, Corinthian currants, derived from a specific type of black grape, are characterized by a low to moderate glycemic index [ 21 ] and an abundance in minerals, vitamins, fiber, flavonoids and phenolics [ 22 , 23 ]. Ongoing research on potential antimicrobial properties of several Mediterranean foods, such as raisins and olive products, should be considered in the context of current research efforts to elucidate any protective effects of flavonoids and other polyphenols against the coronavirus infection [ 24 , 25 ].…”

Food policy, nutrition and nutraceuticals in the prevention and management of COVID-19: Advice for healthcare professionals

“… A Double-blind, Randomized, Controlled Study 50 participants (18 Years and adult, older adult) 500 mg and 1000 mg for group-1 and group-2. Dietary Supplement: Quercetin Prophylaxis/12 weeks (Phase 1) Immune system modulatory www.clinical trials.gov Polyphenols from Broussonetia papyrifera – Evaluation of the inhibitory activities of polyphenols against MERS- and SARS-CoV proteases – Compounds were individually tested at concentrations ranging from 0 to 200 μM – All the tested compounds had a dose-dependent inhibitory activity on SARS-CoV protease with an IC50 ranging from 30.2 to 233.3 μM Annunziata et al (2020) Forsythoside A from Forsythia suspense – CEK cells infected with IBV – Forsythoside A 0.16 mM, 0.32 mM, and 0.64 mM – (i) dose-dependent viral load reduction, (ii) IBV nucleocapsid protein expression reduction and (iii) dose-dependent inhibition of IBV infection Annunziata et al (2020) (−)-catechin gallate and (−)-gallocatechin gallate – Quantum dots-conjugated oligonucleotide system used for the inhibitor screening of SARS-CoV nucleocapsid proteins – – – Marked anti-SARS-CoV nucleocapsid protein activity. In particular, (i) dose-dependently ability to attenuate the binding activity at concentrations≥0.005 μg/ml, (ii) more than 40% inhibition activity at 0.05 μg/ml and (iii) IC50 at the same concentration Annunziata et al (2020) Elderberry The treatment of influenza Non-randomized, double-blind trial 100 participants at the age of 20–65 (female) 15 cc 4 times daily for 5 days Dietary Supplement/Phase 4 www.clinical trials.gov Crude polyphenolic extract from Sambucus nigra …”

“…Nowadays, Sambucus nigra L., widely known as black elderberries which exhibits antimicrobial, antioxidant, antiinflammatory effect in vitro and in vivo ( Chen et al, 2014 ). Previous studies demonstrated that the phenolic compounds of elderberries can inhibit the penetration of influenza virions in vitro ( Annunziata et al, 2020 ; Yasmin et al, 2020 ). This herbal extract, which is generally used among the moher under the observation of doctors, is sold with Vitamin C as syrup or effervescent tablet.…”