For the first time in the history of anti-AIDS research a new promising molecule is being developed which targets both, the Human Immunodeficiency Virus (HIV) and bacteria causing infection in a patient in the advanced stages of AIDS.
The molecule developed by well-known scientist Dr Bhola Vithal Shetty of the National Institutes of Health (NIH), US, is described as 'TAT Antagonist' by the scientist, which works on the basis of 'dual mechanism action' i.e. a single molecule targetting the virus and at the same time attacking a host of bacteria like Pneumocystis Cariini (PCP), E. coli, as well as the microbials linked to Kaposi Sarcoma (KS) etc. which emerge during the advanced stages of HIV infection.
The molecule has entered the advanced stages of in vitro testing in the US, showing promising results. "The drug has shown positive results in early in vitro studies. Currently we are in the midst of doing repetitive and confirmatory in vitro studies in US. We are also in talks with several private research institutes in Pune and Bangalore for doing in vitro tests. In another six months time, we should be starting tests on animals like mice, rabbits and dogs and phase I clinical trials after that," said Dr. Shetty. The molecule has been applied for global patent with some more patents in the pipeline.
According to him, out of the nine genes of an HIV virus, only two genes - TAT and REV - are critical in nature. The function of latter gene is complimentary to that of former and a destruction of the former gene would automatically collapse the latter. "My molecule will have two warheads - one for destroying the TAT gene, which is highly critical in the replication of the virus and the other for destroying bacteria causing infection in advance stages of HIV. The molecule is developed to make it 100 per cent effective against both bacteria and virus," said Dr. Shetty.
As a result, the molecule will be more effective for patients in advanced stages of infection, when a patient dies not from HIV but from bacteria causing infection, where the existing therapies become ineffective to treat. Available drugs like the reverse transcriptase inhibitors, protease inhibitors, invertase inhibitors and the recent fusion inhibitors only try to inhibit the functions of the virus and not virus as whole. As a result the disease can only be controlled and not eliminated. Moreover, antibiotics have to be taken separately to tackle bacterial infections.
The molecule is being designed to penetrate the lymphoid tissue and central nervous system, which shows 98 per cent of total viral density, in an infected person. The molecule has one part as cytopathic inhibitor and other part as gyrase inhibitor, both working synergistically.
Scientists have known about the critical nature of TAT gene and big companies have tried earlier to make TAT antagonists. However as a result of low therapeutic index and heavy toxicity levels in their molecules, they had to abort their projects mid-way.
Dr. Shetty completed his BS, MS and PhD in medicinal chemistry from University of Pennsylvania, Philadelphia. He had a brilliant career with the pharmaceutical industry in companies like Wyeth Medical Research Institute, Pennwalt Institute, and Purdue Pharma, as well as the US FDA for 40 years. For the past several years Dr. Shetty has been carrying out research on AIDS at National institutes of health in Bethesda, Maryland.
He is currently in India as a technical consultant to Mumbai-based Centaur Pharmaceuticals. Centaur will launch Metolazon and a slew of other products discovered by Dr. Shetty in India. Dr. Shetty has been the discoverer of molecules like Metolazon (diuretic) and Ionamin Resin (anti-obesity). Besides he has patented his other discoveries like benzazepirehydrochloride (analgesic), gemo anti-pod (narcotics), BVS - 48C (antibacterial), polydextrose iodine complex (anti-bacterial), which are in various stages of clinical trials across US.