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.