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About the Project
Coronavirus now labelled as Covid-19 has become a global pandemic affecting around 200 countries. Currently neither any cure nor any vaccine for Covid-19 has been established. The major objectives of current approaches are to improve symptoms, maintain essential requirements of life support like oxygen saturation and treatment of secondary microbial infections and organ failure. Hence there is an urgent need to identify novel therapeutic intervention. Attempts have been made to develop new agents for Covid-19, which are now in phase I-III clinical trials. These include hydroxychloroquine, remdesivir, oseltamivir, ASC09F (HIV protease inhibitor), lopinavir, ritonavir, darunavir, and cobicistat. However, they are far from achieving routine clinical success.
Current drug discovery attempts for Covid-19 have severely been hampered due to the lack of cell-free and live virus free high-throughput assay systems. To overcome these limitations, in silico drug screening targeting viral and human ACE2 receptor proteins and structure and network-based design against specific viral proteins have been initiated. However, these approaches suffer from numerous intrinsic variables including obtaining three dimensional structure of the target proteins, lack of reliable docking and soring systems and moreover, they require further extensive experimental validation.
We have previously developed high-throughput splicing assays, screened thousands of natural products and established drugs and identified novel hits for a number of disorders including pulmonary arterial hypertension (PAH) and myelodysplastic syndrome (MDS). The major objectives of this project are (i) develop high-throughput assay systems and screen natural products, (ii) investigate the molecular mechanisms by which the viral proteins may contribute to disease pathogenesis, and (iii) determine whether natural products may provide therapeutic intervention.
The project will introduce the student to the broader areas of molecular genetics, biochemistry, drug discovery, pharmacology and translational medicine. The research activities will be undertaken at the School of Pharmacy and Medical Sciences, University of Bradford. The studies will be performed in the recently renovated laboratories provided with state of the art equipments including high-throughput fluorescence and luminescence plate readers, QPCR machines, gel doc systems and modern tissue culture facilities. The research sits in the context of a highly active research environment at the University of Bradford.
Current drug discovery attempts for Covid-19 have severely been hampered due to the lack of cell-free and live virus free high-throughput assay systems. To overcome these limitations, in silico drug screening targeting viral and human ACE2 receptor proteins and structure and network-based design against specific viral proteins have been initiated. However, these approaches suffer from numerous intrinsic variables including obtaining three dimensional structure of the target proteins, lack of reliable docking and soring systems and moreover, they require further extensive experimental validation.
We have previously developed high-throughput splicing assays, screened thousands of natural products and established drugs and identified novel hits for a number of disorders including pulmonary arterial hypertension (PAH) and myelodysplastic syndrome (MDS). The major objectives of this project are (i) develop high-throughput assay systems and screen natural products, (ii) investigate the molecular mechanisms by which the viral proteins may contribute to disease pathogenesis, and (iii) determine whether natural products may provide therapeutic intervention.
The project will introduce the student to the broader areas of molecular genetics, biochemistry, drug discovery, pharmacology and translational medicine. The research activities will be undertaken at the School of Pharmacy and Medical Sciences, University of Bradford. The studies will be performed in the recently renovated laboratories provided with state of the art equipments including high-throughput fluorescence and luminescence plate readers, QPCR machines, gel doc systems and modern tissue culture facilities. The research sits in the context of a highly active research environment at the University of Bradford.
Funding Notes
This is a self-funded project; applicants will be expected to pay their own fees or have access to suitable third-party funding, such as the Doctoral Loan from Student Finance. In addition to the university's standard tuition fees, bench fees may also apply to this project.
References
Anti Infect Ther, 2020: p. 1-11.
2. Thakur, N., A. Qureshi, and M. Kumar, AVPpred: collection and prediction of highly effective antiviral peptides. Nucleic Acids Res, 2012. 40(Web Server issue): p. W199-204.
3. Zumla, A., et al., Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov, 2016. 15(5): p. 327-47.
4. Nasim, M.T., et al., HnRNP G and Tra2beta: opposite effects on splicing matched by antagonism in RNA binding. Hum Mol Genet, 2003. 12(11): p. 1337-48.
5. Nasim, M.T., H.M. Chowdhury, and I.C. Eperon, A double reporter assay for detecting changes in the ratio of spliced and unspliced mRNA in mammalian cells. Nucleic Acids Res, 2002. 30(20): p. e109.
6. Nasim, M.T. and I.C. Eperon, A double-reporter splicing assay for determining splicing efficiency in mammalian cells. Nat Protoc, 2006. 1(2): p. 1022-8.
2. Thakur, N., A. Qureshi, and M. Kumar, AVPpred: collection and prediction of highly effective antiviral peptides. Nucleic Acids Res, 2012. 40(Web Server issue): p. W199-204.
3. Zumla, A., et al., Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov, 2016. 15(5): p. 327-47.
4. Nasim, M.T., et al., HnRNP G and Tra2beta: opposite effects on splicing matched by antagonism in RNA binding. Hum Mol Genet, 2003. 12(11): p. 1337-48.
5. Nasim, M.T., H.M. Chowdhury, and I.C. Eperon, A double reporter assay for detecting changes in the ratio of spliced and unspliced mRNA in mammalian cells. Nucleic Acids Res, 2002. 30(20): p. e109.
6. Nasim, M.T. and I.C. Eperon, A double-reporter splicing assay for determining splicing efficiency in mammalian cells. Nat Protoc, 2006. 1(2): p. 1022-8.
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