Abstract
Balanced nutrition and appropriate dietary interventions are fundamental in the prevention and management of viral infections. Additionally, accurate modulation of the inflammatory response is necessary to achieve an adequate antiviral immune response. Many studies, both in vitro with mammalian cells and in vivo with small animal models, have highlighted the antiviral properties of resveratrol, rapamycin and metformin. The current review outlines the mechanisms of action of these three important compounds on the cellular pathways involved with viral replication and the mechanisms of virus-related diseases, as well as the current status of their clinical use.
Highlights
Inhibition of important gene pathways like the NF-κB pathway supports its use as an antioxidant, while inhibitions of viral replication, protein synthesis, gene expression and nucleic acid synthesis support its use as an antiviral [30]
Administration of resveratrol resulted in 39% increase of the expression of cleaved caspase-3, a marker of apoptosis, in a phase I study in patients with hepatic metastases in malignant hepatic tissue, as compared with tissues from the patients treated with placebo [135], indicating a potential better response
Metformin has been proposed as a potential coadjuvant treatment for COVID-19 patients [194,195,196]; this hypothesis is further supported by the fact that metformin can both reduce levels of IL-6 [197] and directly act on the pathways increasing cellular pH and subsequently interfering with the endocytic cycle, reducing viral replication [198,199]
Summary
Resveratrol (trans-3,4,5-trihydroxystilbene) is a small polyphenol natural molecule that can be obtained from several sources, including red wine, grapes, a variety of berries, peanuts and certain medicinal plants [1,2]. A number of in vitro data generated in different cancer cell lines, including stomach [98], colorectal [99], intestine [100], liver [101,102,103], kidney [104], blood [105,106,107,108], lung [109,110,111], ovaries [112,113], prostate [114,115], breast [116], glioma cells [117,118,119,120], head and neck tumors [121,122], bone [123], skin [124] and heart [125], as well as experiments in vivo in several animal models [19,126], have shown the anticancer mechanisms of resveratrol [127] and supported its use for cancer prevention due to its direct antitumor effects [128,129,130,131,132]. Treatment with resveratrol resulted in decreased levels of the specific oncogenic miRNAs targeting genes involved in the regulation of both tumor suppressors and effectors of the TGFβ-dependent signaling pathway [92,144,145,146,147]
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