Resveratrol-zinc nanoparticles or pterostilbene-zinc: Potential COVID-19 mono and adjuvant therapy

Abstract

In this manuscript we provide the scientific basis to adopt a novel combination of two widely available nutraceuticals; resveratrol and zinc in management of COVID-19 recommending their administration using a nano-carrier based drug-delivery system. Resveratrol, a well-known antioxidant and anti-inflammatory triphenolic stilbene, is abundant in red grapes, red wine, dark chocolate, and peanut butter. Alternatively, pterostilbene-zinc combination might be also considered without using a nano-carrier. We recommend conducting prompt clinical trials to assess the potential of the suggested combinations as a monotherapy for mild COVID-19 with a potential to prevent its progression to moderate-severe disease for which we recommend their trial as an adjuvant therapy. Furthermore, the suggested combinations might also possess a pharmacotherapeutic potential that exceeds COVID-19 to various inflammatory, immunologic, and oncologic diseases.

The potential role of resveratrol as supportive antiviral in treating conditions such as COVID-19 – A formulator’s perspective

“…Different combinations and formulations with resveratrol are being investigated for COVID-19 e.g., a resveratrol-zinc nanoparticle drug-delivery system [63] , liposome technology, nano emulsions, micelle solid dispersions [64] , [65] , [66] as well as a different route of administration i.e., inhalation [67] , all with the aim of increasing effectiveness by improving its bioavailability. Chemically modified resveratrol analogs and precursors are also investigated.…”

Potential metal-related strategies for prevention and treatment of COVID-19

“…As is known to all, some trace metal elements benefit from regulating the body’s immune response and enhancing resistance [ 27 , 29 – 33 , 35 , 36 ]. Therefore, metal nutrients will play an essential and beneficial role in alleviating excessive inflammation and producing neutralizing antibodies.…”

“…(2) Metal-related drugs play a synergistic effect: enhance the efficacy of antiviral drugs; vaccine adjuvants; and topical antiviral materials. (3) A metal antiviral hydrogel is proposed as a promising method to combat COVID-19 [ 29 – 31 ].…”

“…Metallodrugs are known to play an important role in direct antiviral or inhibiting critical enzymes in the process of virus replication for the SARS-CoV-2 infection [ 27 , 28 ]. Metallodrugs can also be used as adjuvant drugs to enhance the efficacy of antiviral drugs (such as zinc plus hydroxychloroquine) [ 29 – 31 ] or used as vaccine adjuvants [ 32 , 33 ]. It has been illustrated that many metal nanoparticles and metal complexes exhibit excellent anti-inflammatory and antiviral activities [ 27 , 28 ].…”

A Brief Updated Review of Advances to Enhance Resveratrol’s Bioavailability

“…These may therefore be promising antiviral agents against SARS-CoV-2 and should be investigated further in clinical trials. A novel administration of an RES and zinc combination using nano-carrier delivery systems, or a pterostilbene-zinc Molecules 2021, 26, 4367 2 of 8 combination without a nano-carrier system, have both been suggested as possible mono and adjunct therapies for mild COVID-19 [9].…”