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Development of novel types of small molecule inhibitors against HIV

2009년 8월 17일 18시 32분 48초
목18F4심 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
목 15시 : 20분
의약화학 - Current Struggles against Infectious Diseases
저자 및
가톨릭대학교 성의교정 병리학교실, Korea
The Human Immunodeficiency virus(HIV), a causative agent of AIDS(Acquired Immune Deficiency Syndrome), is a lentivirus containing about a 10Kb RNA genome. The viral genomic RNA packaging, or alternatively known as encapsidation, into viral particles from its host cells is a formidable task for the sake of viruses. It is especially important for RNA viruses as they have to discriminate the viral RNA from a pool of numerous cellular RNAs.The components involved in the packaging of the HIV viral genomic RNA during virion assembly is believed to be mediated by a specific interaction between the Nucleocapsid(NC) in the gag polyprotein and a packaging sequence, so-called psi(ψ), located near the 5'-end of LTR(long terminal repeat) region of the viral genome. In addition to having this essential role, the NC protein has been known to be involved in many other important steps in the viral life cycle such as the viral reverse transcription, translocation of PIC (pre-integration complex) into host nucleus, integration, and gene expression stages.Moreover, as being "mutation non-permissive" in its nature, the NC protein has been emerged as a highly promising target for the development of new types of anti-HIV inhibitor.Yet, the identification and development of such molecules has been hampered in part due to a lack of a functional assay for the NC protein.By exploiting a novel functional cell-based assay that probes the specific protein-RNA interaction between the NC protein and psi(ψ) RNA, we are able to not only to decipher and dissect the specific interaction of the HIV NC-psi(ψ) RNA in vivo, but also to identify for the first time a novel types of anti-HIV small molecules targeting the NC and NC-Psi interaction. The significance of the results and usefulness of our system for developing other antiviral agents will be presented