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The University of Hyderabad (UoH) has been granted a patent “Novel anti-HIV-1 heteroaromatic compounds targeted to HIV-1 associated Topoisomerase II beta kinase” – The discovery of new compound has been accomplished through the efforts made by team under supervision of Prof. Anand K. Kondapi for treatment of HIV-1 infection as a new line of therapy, in the Laboratory for Molecular Therapeutics, Department of Biotechnology and Bioinformatics, School of Life Sciences.

Human immunodeficiency virus type I (HIV-1), a causative agent for AIDS (acquired immunodeficiency syndrome), infects human T helper cells and replicates with the help of host and viral proteins. Topoisomerase II β, is an enzyme shown to be involved in HIV-1 reverse transcription and integration. HIV-1-associated Topoisomerase II beta kinase (TopoIIβKHIV-1) phosphorylates host Topoisomerase II β at its serine residues and promotes HIV-1 reverse transcription. The present results of analysis of anti-HIV-1 activity and Topoisomerase II β kinase antagonism of pyridine derivatives yielded coumarin, as an important pharmacophore based on medicinal chemistry. Further, evaluation of the structure-activity relationships (SARs) of coumarin derivatives in silico and in vitro led to the current invention.

The current novel anti-HIV-1 drug candidates were prepared in a two-step process; the first one follows an eco-friendly green chemistry process involving water as solvent, while in the second step a salt is formed. This result of this invention brings out several novel features such as, water solubility of the drug candidates, non-toxic and higher anti-HIV-1 activity at nanomolar concentrations with picomolar antagonism against TopoIIβKHIV-1 (a novel target discovered in the lab) leading to a highly significant inhibition of virus replication by blocking HIV-1 dsDNA synthesis during reverse transcription (as shown in model).

The research team actively working in the research and development of these drugs are Kurumurthy Kammari, Akhila Bommakanti,  Kiran Devaraya, Satyajit Mukhopadhyay and Sarita Swain.

             

Kurumurthy Kammari                                             Akhila Bommakanti

                 

Kiran Devaraya                                            Satyajit Mukhopadhyay