Aigerim Kassym, Ramsha Khalid, Syed Abidi and Syed Ali
Nazarbayev University School of Medicine, Kazakhstan
Aga Khan University, Pakistan
Posters & Accepted Abstracts: Med Chem
Background: Hepatocellular carcinoma (HCC) is the most prevalent type of primary liver cancer and the second leading cause
of cancer death globally. The principal risk factor for HCC is chronic infection with hepatitis C or B virus. Although direct-acting
antivirals are effective in reducing viral load in chronic hepatitis, Hepatitis C virus (HCV) infected patients still remain at risk of
developing HCC. Therefore, new therapeutic strategies need to be developed for this detrimental condition. Recently, it was found
that Ruvbl2, an ATP-dependent DNA helicase, is overexpressed in HCC and is associated with poor prognosis. On the other hand,
HCV also utilizes a helicase, NS3, to replicate its genome. These human and viral helicases share evolutionarily conserved motifs
that are involved in important functions of the enzyme. Here, we propose simultaneous targeting of HCV helicase NS3 and human
helicase Ruvbl2 in the liver for, respectively, treating HCV infection and preventing HCC.
Objective: The primary objective of this study was to identify and functionally characterize evolutionarily conserved amino acid sequence motifs in HCV helicase NS3 and human helicase Ruvbl2.
Methodology: To identify conserved motifs in NS3 and Ruvbl2, we used the MEME computational tool. To discover the functions of the motifs, we performed a literature search and protein structure analysis. Location of the motifs in the protein 3D structures was performed using the Discovery Studio software.
Result: We have found 10 evolutionarily conserved, functionally important motifs in NS3 and Ruvbl2 involved in ATP and/or substrate binding.
Conclusion: The evolutionarily conserved motifs we identified here may be used as targets for the future design of next-generation drugs that could be used for simultaneous treatment of HCV infection and HCC
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