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SummaryHIV-1 causes diverse immunomodulatory responses in the host, including the down-regulation... more SummaryHIV-1 causes diverse immunomodulatory responses in the host, including the down-regulation of co-stimulatory proteins CD80/86, mediated by HIV-1 protein Nef, blunting T-cell activation. Using a screening cascade of biochemical and cell-based assays, we identified potent small molecules representing three chemical scaffolds namely amino pyrimidine, phenoxy acetamide and bi-aryl heteroaryl carbamate which target the protein-protein interaction interface of CD80/86 and Nef with sub-micromolar potency. These molecules restore CD80/86 surface levels in HIV-1-Nef infected antigen presenting cells and T-cell activation. Nef-CD80 interface and small molecule binding sites were mapped by using computational docking and structural studies, followed by validation by mutational analysis. This analysis resulted in the identification of two key residues, K99 and R111, which were associated with down-modulation of CD80 surface levels by Nef and important for small molecule binding. Targetin...
The growth of Indian pharmaceutical industry has been characterized by extensive governmental con... more The growth of Indian pharmaceutical industry has been characterized by extensive governmental control and absence of strong patent protection. This paper gives an overview of pharmaceutical industry in India and the likely impact of product patent regime on it. The analysis is based on secondary data published elsewhere. It also reviews the existing patent and drug control laws in India and how they have affected the growth and structure of pharmaceutical industry in the country. Also discussed are strategies to meet the new challenges and the opportunities that Trade-Related Aspects of Intellectual Property Rights (TRIPS) Agreement presents to pharmaceutical industry in India.
The growth of Indian pharmaceutical industry has been characterized by extensive governmental con... more The growth of Indian pharmaceutical industry has been characterized by extensive governmental control and absence of strong patent protection. This paper gives an overview of pharmaceutical industry in India and the likely impact of product patent regime on it. The analysis is based on secondary data published elsewhere. It also reviews the existing patent and drug control laws in India and how they have affected the growth and structure of pharmaceutical industry in the country. Also discussed are strategies to meet the new challenges and the opportunities that Trade-Related Aspects of Intellectual Property Rights (TRIPS) Agreement presents to pharmaceutical industry in India.
SummaryHIV-1 causes diverse immunomodulatory responses in the host, including the down-regulation... more SummaryHIV-1 causes diverse immunomodulatory responses in the host, including the down-regulation of co-stimulatory proteins CD80/86, mediated by HIV-1 protein Nef, blunting T-cell activation. Using a screening cascade of biochemical and cell-based assays, we identified potent small molecules representing three chemical scaffolds namely amino pyrimidine, phenoxy acetamide and bi-aryl heteroaryl carbamate which target the protein-protein interaction interface of CD80/86 and Nef with sub-micromolar potency. These molecules restore CD80/86 surface levels in HIV-1-Nef infected antigen presenting cells and T-cell activation. Nef-CD80 interface and small molecule binding sites were mapped by using computational docking and structural studies, followed by validation by mutational analysis. This analysis resulted in the identification of two key residues, K99 and R111, which were associated with down-modulation of CD80 surface levels by Nef and important for small molecule binding. Targetin...
The growth of Indian pharmaceutical industry has been characterized by extensive governmental con... more The growth of Indian pharmaceutical industry has been characterized by extensive governmental control and absence of strong patent protection. This paper gives an overview of pharmaceutical industry in India and the likely impact of product patent regime on it. The analysis is based on secondary data published elsewhere. It also reviews the existing patent and drug control laws in India and how they have affected the growth and structure of pharmaceutical industry in the country. Also discussed are strategies to meet the new challenges and the opportunities that Trade-Related Aspects of Intellectual Property Rights (TRIPS) Agreement presents to pharmaceutical industry in India.
The growth of Indian pharmaceutical industry has been characterized by extensive governmental con... more The growth of Indian pharmaceutical industry has been characterized by extensive governmental control and absence of strong patent protection. This paper gives an overview of pharmaceutical industry in India and the likely impact of product patent regime on it. The analysis is based on secondary data published elsewhere. It also reviews the existing patent and drug control laws in India and how they have affected the growth and structure of pharmaceutical industry in the country. Also discussed are strategies to meet the new challenges and the opportunities that Trade-Related Aspects of Intellectual Property Rights (TRIPS) Agreement presents to pharmaceutical industry in India.