Polyphenols: A Diverse Class of Multi-Target Anti-HIV-1 Agents

Polyphenols are a versatile class of compounds that represent secondary metabolites from higher plants and which are abundantly present in the human diet. Epidemiological data suggest protective effects of polyhenols in relation to cancer, cardiovascular diseases, diabetes, infectious diseases and age-related conditions. HIV/AIDS remains prevalent in many parts of the world as acute infection and as anti-retroviral drug (ARV)-managed chronic disease. Due to the nature of the human immune deficiency virus (HIV) and an increased use of ARVs many drug-resistant HIV strains have emerged and continue to do so. This makes it impossible to rely on one standard drug treatment regime. This review summarizes anti-HIV activities of polyphenols. It highlights the diversity of modes of action by which polyphenols - according to their respective compound classes - exert their activities. Additionally, this review discusses polyphenols as multi-target anti-HIV agents and provides the context of in-vivo and clinical data. Based on the presented data, a three-pronged approach for further anti-HIV drug discovery is suggested applying methods of combinatorial medicinal chemistry on the diverse and sometimes unique scaffolds of polyphenols. The latter being selected according to the approach of 'reverse pharmacology' as a creative way to place safety and other clinical consideration at the beginning of the drug discovery- and development process.