【摘 要】
：
Dengue virus type 2 (DEN2) NS3 protease is required for the processing of the viral polyprotein and viral maturation.Therefore, the NS3 protease represents a promising target for antiviral drug design
【机 构】
：
Laboratory of Molecular Virology, Institute of Molecular Biology and Genetics, Mahidol University, S
【出 处】
：
2005 WHTS3rd Annual Congress of International Drug Discovery
论文部分内容阅读
Dengue virus type 2 (DEN2) NS3 protease is required for the processing of the viral polyprotein and viral maturation.Therefore, the NS3 protease represents a promising target for antiviral drug design and development.In this study, we show that the N-terminal cleavage site peptides corresponding to the P1-P6 region (RTSKKR, EVKKQR, FAAGRK and TTSTRR) act as competitive inhibitors of the enzyme, with Ki values ranging from 12 to 67 M.The peptide RTSKKR has the lowest Ki (12.14 M) and was used to analyze shorter peptides including SKKR, KKR, KR, AGRR and GKR.The results show that SKKR, KKR, KR, and GKR act as competitive inhibitors of the enzyme, with Ki values ranging from 22 to 188 M.By using the crystal structure coordinates of the hepatitis C virus NS3/NS4A protease complex, we have developed a homology model of the DEN 2 NS2B(H)-NS3(pro) co-complex.With 2 protein structures and 9 peptide substrates aforementioned, molecular docking has been performed to investigate the substrate binding site of NS3.The results show that the cofactor NS2B(H) induces large structural changes in the NS3 protease.These results offer the prospect of developing potent inhibitors by combinatorial chemistry based on the structure of native cleavage site peptides.
其他文献
Today the number of unique chemical compounds available for screening on the commercial basis is about twenty millions.The number of potential pharmacological targets is quickly growing due to the ach
Osteoporosis is a bone disease most commonly found amongst the elderly females than in males.In the affected patients the amount of bone destruction is higher than its formation.This leads to bone los
Modulation of signaling pathways and gene expression is an important approach in the treatment of autoimmune and inflammatory disorders.This presentation will focus on the development of drugs that in
To develop new antibiotics, evaluation of their therapeutic effect using animal model is essential.Mice have been used for decades, however, the use of mice creates ethical and cost problems.To overco
Resistance of bacteria to antibiotics has become one of the main problems in human health.The discovery of new antibiotic families is a way to circumvent such problems and antimicrobial peptides may r
We have developed a technical platform composing a high density peptide array and a computer algorithms that can be used to screen, identify, and design peptides for specific targeting in a high throu
The presentation will be focused on application of advanced in vitro technologies, especially in vitro models based on human and animal tissues, and strategies into new discovery and development of ne
One of the most critical drug evaluation systems is a pre-clinical evaluation for absorption, distribution, metabolism and elimination and toxicity (ADMET), which has been demonstrated to cause approx
For the production of organic nanocomposites the spray freeze drying technique seems to be the process of choice for temperature and structure sensitive drugs of biological origin such as Interferons.
The Industrial Pharmacy Lab (IPL) is focusing on research in process technology and pharmaceutical drug formulation.This research is very close to the todays needs of the pharmaceutical industry looki