IN SILICO ANTIMALARIAL SCREENING OF THE PHYTOCONSTITUENTS OF SOME LOCAL FOOD SPICES AGAINST PLASMEPSIN II

Abstract

Food spices such as Aframomum sceptrum and Ricinodendron heudelotti have been identified to be useful in managing malaria through in vitro studies. This study aims to investigate the antimalarial potential of Aframomum sceptrum and Ricinodendron heudelotti through in silico studies. Phytoconstituents present in these food spices were obtained from GC/MS analysis, and their 2D and 3D SDF structures were obtained from PubChem. The protein target Plasmepsin II receptor (ILF3) was obtained from Protein Data Bank and prepared using Biovia Discovery Studio 2020; afterwards, molecular docking was done using PyRx. Post docking analysis was done using Biovia Discovery Studio 2020, and ADMET profiling using the Swiss ADME webserver and ProTox-III virtual lab. Twenty (20) of the phytoconstituents present in Aframomum sceptrum and twenty (20) of the phytoconstituents present in Ricinodendron heudelotti all had binding affinity values of less than or equal to -6.5 kcal/mol against the target protein. On completion of ADMET profiling and postdocking analysis of the phytoconstituents, it was shown that some of these phytoconstituents showed in silico antimalarial activity which validated their use traditionally for the treatment of malaria when compared with a standard drug (Artesunate). However some of these phytoconstituents may not progress to drug development stage due to their toxicity profiles. Some of the phytoconstituents showed major organ toxicities, hence further research is needed to improve the safety and efficacy of these phytoconstituents, either through chemical modifications or by exploring alternative compounds with similar binding affinities and lower toxicity. Compounds 18 and 19 from Aframomum sceptrum showed good binding affinity values - 8.6 Kcal/mol, while 10, 11, 12, and 18 had binding affinity values comparable to Artesunate the positive control antimalarial agent used in this study. This study validates the ethnomedicinal uses of these plants extract in the treatment of malarial and other diseases. Further in vivo and isolation studies are required to identify the phytoconstituents with antimalarial activity.