Antiviral alkaloid principles of the plant family Amaryllidaceae

Abstract

BackgroundViral-borne diseases are amongst the oldest diseases known to mankind. They are responsible for some of the most ravaging effects wrought on human health and well-being. The use of plants against these ailments is entrenched in both traditional and secular medicine around the globe. Their natural abundance and chemical diversity have also boosted their appeal in drug discovery. AimThe plant family Amaryllidaceae is distinguished for its alkaloid principles, some of which are of considerable interest in the clinical arena. This account is the outcome of a literature review undertaken to establish the applicability of these substances as antiviral agents. MethodsThe survey utilized the search engines Google Scholar, PubMed, SciFinder, Scopus and Web of Science engaging the word ‘antiviral’ in conjunction with ‘Amaryllidaceae’ and ‘Amaryllidaceae alkaloid’. The search returned over five hundred hits, of which around eighty were of relevance to the theme of the text. ResultsOver eighty isoquinoline alkaloids have been screened against nearly fifty pathogens from fourteen viral families, the majority of which were RNA viruses. Potent activities were reported in some instances, such as that of trans-dihydronarciclasine against Yellow fever virus (IC50 0.003 μg/ml), with minimal effects being manifested on host cells. There were also promising results obtained from in vivo studies, in most cases without lethal effects on test subjects. Structure-activity relationship studies afforded useful insight to the antiviral pharmacophore, with the phenanthridone alkaloid nucleus shown to be the most enabling. Although the mechanistic basis to these activities pertained mostly to inhibition of DNA, RNA and protein synthesis, evidence was also forthcoming about the inhibitory action of some of the alkaloids against viral neuraminidase, protease and reverse transcriptase. In silico methods of analysis have offered further perspectives of how some of the alkaloids interact at the active sites of their targets. ConclusionThe Amaryllidaceae offers a viable platform for plant-based antiviral drug discovery. Its cause is strengthened not only by its wide proliferation and exploitation of its members in alternative forms of medicine, but also by its rich chemical diversity which has already spawned useful antiviral drug leads.