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Assessment of Plasmodium Falciparum RNA Pseudouridylate Synthase (Putative) as Novel Drug Target

Muhammad, Aliyu and Rotimi, S. O and Jelili, Oyelade and Isewon, Itunuoluwa and Ventura, Barbara Di and Eils, Roland and Lanzer, Michael and Brors, Benedikt and Adebiyi, Ezekiel (2016) Assessment of Plasmodium Falciparum RNA Pseudouridylate Synthase (Putative) as Novel Drug Target. In: 3rd International Conference On African Development Issues (CU-ICADI), May 9- May 11 2016, Covenant University, Ota, Nigeria.

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Malaria is a major public health problem associated with high mortality, morbidity rates and undue economic burden in sub-Saharan countries. Presently, every year, 300 to 500 million people suffer clinically from malaria and 90% of them in sub-Saharan Africa. About 1.5 to 3 million people die of malaria every year and 85% of these occur in Africa. One child dies of malaria somewhere in Africa every 20 second, and there is one malarial death every 12 sec somewhere in the world. This is also a damaging economic burden for these sub-Saharan Africa countries as huge work force time and resources are expended for treatment. Plasmodium falciparum (hence forth Pf) is the most severe of all the human malaria parasites. This organism is continuing to develop resistance to all known drugs and therapeutic regime. One of the mechanisms of resistance in Pf is the modification of the drug target. Hence, it is expedient to continuously discover novel drug targets in Pf and to discover or develop new drugs against such targets. Drug-able signaling pathways have been shown to have inherent mechanism capable of deterring drug resistance. Using computational techniques, we have identified some proteins in the signaling pathways of Pf as putative targets for anti-plasmodia drug. RNA pseudouridylate synthase, which also plays a key role in RNA synthesis and ribosomal function, is one of such proteins. Initial virtual screening of this enzyme against drug and chemical databases has been performed to identify compounds that can inhibit this enzyme. This led us to compounds which inhibit nucleotide metabolism. This is a work in progress whose current state is hoped for presentation at this conference. In order to determine the identified compounds IC50, the identified compounds will be screened in vitro against the enzyme. We have currently completed the establishment of the enzyme functionally expression in E. coli and purification. Thereafter, the drugs will be screened for their anti-plasmodia activity using cultured Pf and the IC50 for each drug will be determined. In order to assess their safety, the selectivity index of compounds that showed in vitro anti-plasmodia activity will be determined using human cultured cell lines. The last stage of this study will involve screening the compounds in an in vivo mouse model of malaria. It is hoped that the result of this study will prove this enzyme as a novel target for antimalarial drug. And provide as input, critical drug targets in to our established Structure Based Drug Design (SBDD) pipeline

Item Type: Conference or Workshop Item (Paper)
Uncontrolled Keywords: Drug design, Plasmodium falciparum, RNA pseudouridylate synthase, drug target, Virtual Screening, anti-plasmodial
Subjects: Q Science > QA Mathematics > QA75 Electronic computers. Computer science
Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Medicine, Health and Life Sciences > School of Biological Sciences
Depositing User: Mrs Hannah Akinwumi
Date Deposited: 28 Jun 2016 07:35
Last Modified: 28 Jun 2016 07:35

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