Stand Up to Stand Out: Natural Dietary Polyphenols Curcumin, Resveratrol, and Gossypol as Potential Therapeutic Candidates against Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Abstract

The COVID-19 pandemic has stimulated collaborative drug discovery efforts in academia and the industry with the aim of developing therapies and vaccines that target SARS-CoV-2. Several novel therapies have been approved and deployed in the last three years. However, their clinical application has revealed limitations due to the rapid emergence of viral variants. Therefore, the development of next-generation SARS-CoV-2 therapeutic agents with a high potency and safety profile remains a high priority for global health. Increasing awareness of the “back to nature” approach for improving human health has prompted renewed interest in natural products, especially dietary polyphenols, as an additional therapeutic strategy to treat SARS-CoV-2 patients, owing to its good safety profile, exceptional nutritional value, health-promoting benefits (including potential antiviral properties), affordability, and availability. Herein, we describe the biological properties and pleiotropic molecular mechanisms of dietary polyphenols curcumin, resveratrol, and gossypol as inhibitors against SARS-CoV-2 and its variants as observed in in vitro and in vivo studies. Based on the advantages and disadvantages of dietary polyphenols and to obtain maximal benefits, several strategies such as nanotechnology (e.g., curcumin-incorporated nanofibrous membranes with antibacterial-antiviral ability), lead optimization (e.g., a methylated analog of curcumin), combination therapies (e.g., a specific combination of plant extracts and micronutrients), and broad-spectrum activities (e.g., gossypol broadly inhibits coronaviruses) have also been emphasized as positive factors in the facilitation of anti-SARS-CoV-2 drug development to support effective long-term pandemic management and control.

Hydroxytyrosol Counteracts Triple Negative Breast Cancer Cell Dissemination via Its Copper Complexing Properties

“…Polyphenols are a group of naturally occurring compounds found in various plantbased foods, such as fruits, vegetables, whole grains, and beverages like tea and red wine [1]. They have gained considerable attention for their potential health benefits and their ability to counteract cancer onset and progression [2].…”

Plant-Derived Epi-Nutraceuticals as Potential Broad-Spectrum Anti-Viral Agents

“…Moreover, a human study in Pakistan evaluated the efficacy and safety of an oral curcumin-quercetin supplement plus standard care vs. standard care alone in outpatients with early-stage COVID-19. The study found that the curcumin-quercetin group had a significantly higher viral clearance (18/25 (72.%)) compared to that of the control group [266]. In addition, curcumin-quercetin reduced acute COVID-19 symptoms in a group compared to a control group [266].…”

“…The study found that the curcumin-quercetin group had a significantly higher viral clearance (18/25 (72.%)) compared to that of the control group [266]. In addition, curcumin-quercetin reduced acute COVID-19 symptoms in a group compared to a control group [266].…”