Ebola Virus Study Generates PhD in Health Sciences

A novel study on the Ebola virus that produced four publications in just one academic year earned Dr Marissa Balmith a PhD in Health Sciences.

Titled: Potential Ebola Virus (EboV) Drug Targets: A Computational Insight into Drug Discovery, the study examined the EboV, an incapacitating virus eventually resulting in the death of infected people.

According to Balmith, the Ebola virus is a severe and often fatal disease and the outbreak in West Africa is the world’s deadliest to date. ‘I was especially intrigued with how the virus moves through its lifecycle and when I first joined Professor Mahmoud Soliman’s research group, he proposed the idea of working on a project on Ebola and the rest is history,’ she said.

Supervised by UKZN’s Dean and Head of the School of Health Sciences Professor Mahmoud Soliman, Balmith’s first report demonstrated a literature review on the Ebola virus from an experimental and computational perspective that aimed to aid in the discovery of Ebola virus inhibitors as well as a comprehensive analysis on all seven Ebola virus proteins.

The second study reported on active site identification of all targets of the Ebola virus. A homology model of the RNA dependent RNA polymerase (RdRp) was put forth and subsequently used for docking purposes.

‘Silico studies performed have revealed precise molecular level understandings of mutations together with their effects on the conformational landscape and dimerization of VP40 of the Ebola virus. In addition to this, the inhibitory mechanism of the compound Imatinib acting on VP40 was investigated,’ said Balmith.

The study reported the first physical model to understand the conformational and mechanistic effect of mutation as well as inhibitor binding landscape of VP40.

Balmith says the results obtained from these studies will provide clear direction for the development of more effective therapeutic interventions against the Ebola virus.

Balmith said the EboV comprises seven key enzymes all of which play a crucial role in the lifecycle of the virus. ‘Elucidating the structure of these enzymes will provide researchers with clues to their functions, accompanied by new ways in which to inhibit their activity using various drugs,’ she said.

According to Balmith, apart from experimental studies, no in silico studies have been performed before to unveil the precise molecular level understanding of mutations and their effects on the conformational landscape of VP40.

Her study employed in silico approaches for the very first time to uncover and understand the conformational changes of VP40 as a result of mutations. In addition to this, the inhibitory mechanism of the compound Imatinib acting on Ebola VP40 was investigated.

‘However, to date, no molecular level understanding or simulation of the possible mechanism of action using accelerated molecular dynamics (aMD) was reported on VP40,’ she declared.

According to Balmith, the work presented in this study will not only describe a precise molecular level understanding of the effect of mutations to the loop region of VP40, but will also provide a comparison of the dynamical landscape between free and inhibitor bound structures of VP40 using aMD simulations.

‘To this end, this study can act as a cornerstone to develop novel chemical entities targeting the EboV,’ she said.

Balmith is currently a post-doctoral research fellow at the Scientific Computing Research Unit at the University of Cape Town under the supervision of Professor Kevin Naidoo and Dr Anwar Jardine. Her field of research involves glycomimetics synthesis for cancer which involves both computational and experimental studies.

‘I am passionate about research and passionate about science. My future aspirations would be to continue to grow as a scientist by bringing innovative ideas and problem solving to research and development sector,’ she added.

By Nombuso Dlamini

Source UKZN