Combining the flavonoid quercetin with the drug fenofibrate as a potential treatment for COVID-19.

Key Messages

This theoretical paper discusses the impact of the drug fenofibrate on cholesterol metabolism in COVID-19 patients as well as the potential interaction of the natural flavonoid quercetin with fenofibrate.

A recent study discovered that fenofibrate inhibits SARS-CoV-2 replication and COVID-19 disease progression by altering cholesterol metabolism in the lung cells of COVID-19 patients.

A preclinical study has shown there is a synergistic effect between fenofibrate and the flavonoid quercetin which reduces the cholesterol content of cells. This effect may be useful for treating COVID-19.

In addition, fenofibrate possesses anti blood-clotting activity, cardiovascular protective properties and the ability to lower plasma fibrinogen levels, which also reduces the likelihood of clotting. All of these properties may be important when treating COVID-19.

Results in Chemistry

Publication Date: January 1, 2021
Peer Reviewed: Yes
Publication Type: Original | Theoretical
DOI: https://www.doi.org/10.1016/j.rechem.2021.100148

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

Anil Pawar, Amit Pal, Kalyan Goswami, Rosanna Squitti, Mauro Rongiolettie

Abstract

There is an urgent need to identify therapeutics for the treatment of Coronavirus disease 2019 (COVID-19). Although different antivirals are given for the clinical management of SARS-CoV-2 infection, their efficacy is still under evaluation. Here, we have screened existing drugs approved for human use in a variety of diseases, to compare how they counteract SARS-CoV-2-induced cytopathic effect and viral replication in vitro. Among the potential 72 antivirals tested herein that were previously proposed to inhibit SARS-CoV-2 infection, only 18 % had an IC50 below 25 µM or 102 IU/ml. These included plitidepsin, novel cathepsin inhibitors, nelfinavir mesylate hydrate, interferon 2-alpha, interferon-gamma, fenofibrate, camostat along the well-known remdesivir and chloroquine derivatives. Plitidepsin was the only clinically approved drug displaying nanomolar efficacy. Four of these families, including novel cathepsin inhibitors, blocked viral entry in a cell—type specific manner. Since the most effective antivirals usually combine therapies that tackle the virus at different steps of infection, we also assessed several drug combinations. Although no particular synergy was found, inhibitory combinations did not reduce their antiviral activity. Thus, these combinations could decrease the potential emergence of resistant viruses. Antivirals prioritized herein identify novel compounds and their mode of action, while independently replicating the activity of a reduced proportion of drugs which are mostly approved for clinical use. Combinations of these drugs should be tested in animal models to inform the design of fast track clinical trials.