Abstract
The acquired immunodeficiency syndrome (AIDS) in humans, which is caused by the human
immunodeficiency virus type 1 (HIV-1) remains among the leading causes of death worldwide. Although
HAART has reduced HIV mortality significantly, adhering to the recommended drug schemes, significant
toxicities experienced by treated patients, and the high mutation rate of the virus that seem to easily circumvent
the action of these drugs emphasize the need for alternative treatment strategies. Medicinal plants are a good
source for the discovery of novel antimicrobial chemotherapeutic agents. Reverse transcription is the most
essential step for viral replication to succeed successfully. This makes reverse transcriptase the prime target for
antiviral therapy against HIV.
Emphasis was placed on the discovery of plants with inhibitory activity against HIV-1 reverse
transcriptase. Crude extracts from the active plant(s) was screened in vitro for their ability to suppress HIV
replication in suitable cell systems. The potential of isolating and identifying the active principle(s) was also
investigated.
Crude extracts from different parts of Gunnera perpensa showed similar amounts of inhibition:
aqueous extracts (97% „b 0.110%SD), methanol/chloroform extracts (94% „b 2.374%SD), rhizome extracts (96%
„b 0.475%SD), stem extracts (94% „b 3.723%SD), leaf extracts (96% „b 1.097% SD). Crude extracts were found to
be significantly (P„T0.027) non-toxic to CEM.NKR.CCR5 cells and PBMCs at 5 ƒÝg/ml. In acutely infected
CEM.NKR.CCR5 cells, acutely infected PBMCs, and chronically infected PBMCs Gunnera perpensa extracts
did not significantly (P>0.05) increase cell viability or reduced HIV core protein content, over 4 days. The in
vitro test did therefore not reflect the findings with the reverse transcriptase assay. Activity-guided fractionations
of Gunnera perpensa rhizome extract lead to the collection of a significantly active fraction. NMR studies
revealed the presence of an epimeric mixture of glucose ¡§contaminants¡¨ in this active fraction. The presence of
these ¡§contaminants¡¨ concealed the true structure of the active principle.
Gunnera perpensa was identified as containing a potential active principle that significantly
inhibits recombinant HIV reverse transcriptase. Unfortunately, in vitro experiments could not confirm this
finding. The identity and structure of the active principle remains unidentified. Future studies will be concerned
with in vitro antiviral studies of the pure active principle. Furthermore, preliminary tests indicated that some of
the original collection of crude extracts had anti-bacterial and anti-malarial activities. These findings can be
investigated in future.
Dr. D. Meyer