A critical evaluation of risk to reward ratio of quercetin supplementation for COVID-19 and associated comorbid conditions.

The interim results of the large, multinational trials on coronavirus disease 2019 (COVID-19) using a combination of antiviral drugs appear to have little to no effect on the 28-day mortality or the in-hospital course. Therefore, there is a still vivid interest in finding alternate re-purposed drugs and nutrition supplements, which can halt or slow the disease severity. We review here the multiple preclinical studies, partially supported by clinical evidence showing the quercetin's possible therapeutic/prophylaxis efficacy against severe acute respiratory syndrome coronavirus (SARS-CoV) as well as comorbidities like chronic obstructive pulmonary disease (COPD), diabetes mellitus, obesity, coagulopathy, and hypertension. Currently, 14 interventional clinical trials are underway assessing the efficacy of quercetin along with other antiviral drugs/nutritional supplements as prophylaxis/treatment option against COVID-19. The present review is tempting to suggest that, based on circumstantial scientific evidence and preliminary clinical data, the flavonoid quercetin can ameliorate COVID-19 infection and symptoms acting in concert on two parallel and independent paths: inhibiting key factors responsible for SARS-CoV-2 infections and mitigating the clinical manifestations of the disease in patients with comorbid conditions. Despite the broad therapeutic properties of quercetin, further high power randomized clinical trials are needed to firmly establish its clinical efficacy against COVID-19.

Molecular basis of quercetin as a plausible common denominator of macrophage-cholesterol-fenofibrate dependent potential COVID-19 treatment axis.

The world's largest randomized control trial against COVID-19 using remdesivir, hydroxychloroquine, lopinavir and interferon-ß1a appeared to have little or no effect on hospitalized COVID-19 patients. This has again led to search for alternate re-purposed drugs and/or effective "add-on" nutritional supplementation, which can complement or enhance the therapeutic effect of re-purposed drug. Focus has been shifted to therapeutic targets of severe acute respiratory syndrome coronavirus (SARS-CoV-2), which includes specific enzymes and regulators of lipid metabolism. Very recently, fenofibrate (cholesterol-lowering drug), suppressed the SARS-CoV-2 replication and pathogenesis by affecting the pathways of lipid metabolism in lung cells of COVID-19 patients. A preclinical study has shown synergistic effect of quercetin (a flavonoid) and fenofibrate in reducing the cholesterol content, which might be useful in COVID-19 treatment. Based on the scientific literature, use of quercetin and fenofibrate in COVID-19 seems meaningful in pharmaceutical and biomedical research, and warrants basic, experimental and clinical studies. In this article, we have summarized the contemporary findings about drug fenofibrate and its effect on membrane synthesis of COVID-19 virus along with emphasizing on possible synergistic effects of quercetin with fenofibrate.

Zinc and COVID-19: Basis of Current Clinical Trials.

Coronavirus disease-2019 (COVID-19) pandemic continues to threaten patients, societies, and economic and healthcare systems around the world. Like many other diseases, the host immune system determines the progress of COVID-19 and fatality. Modulation of inflammatory response and cytokine production using immunonutrition is a novel concept that has been applied to other diseases as well. Zinc, one of the anti-inflammatory and antioxidant micronutrient found in food with well-established role in immunity, is currently being used in some clinical trials against COVID-19. This review integrates the contemporary studies of role of zinc in antiviral immunity along with discussing its potential role against COVID-19, and ongoing COVID-19 clinical trials using zinc.

Hydroxychloroquine and Covid-19: A Cellular and Molecular Biology Based Update.

As the time for finding a definitive and safe cure as a vaccine for novel Corona Virus Disease 2019 (Covid-19) is still far, there is need to study in depth about the other potential drugs, which can save millions of lives due to Covid-19 pandemic. Right at the center of the debate is the use of drug "Hydroxychloroquine" as a prophylaxis as well as a treatment strategy against Covid-19 in conjunction with azithromycin. In this review, we will study the cellular and molecular aspects of hydroxychloroquine, which had driven its use in Covid-19 patients, as well as its chemistry and pharmacokinetics along with clinical trials going on worldwide using hydroxychloroquine against Covid-19.