具有抗病毒作用的红树林耐酸微生物次生代谢产物的研究

Viral diseases like influenza virus and hepatitis B virus?showed?high incidence and seriously affect human health. However, for side effects or easy resistant, until now,there are no specific drugs available for clinical use. New and more effective antiviral agents for future therapy are desired. Based on previous work, this subject will continue to study the anti-virus metabolites of acid-tolerant microorganism of mangroves with anti-influenza virus and anti-HBV model in vitro. Acid samples from mangrove ecosystem will be collected; With different culture conditions at low pH, microorganism including fungi or actinomycetes were isolated from the collected samples; With sequence analysis and morphological analysis, these microorganism will be identified.These microorganism will be screened with chemical methods (TLC or HPLC) and biological activities; Mass fermentation will be conducted.With chromatographic methods (silica gel, Sephadex LH-20 and HPLC), the metabolites will be isolated. By means of modern spectral analysis (NMR, MS, CD, UV, IR), quantum chemical calculations and chemical methods, the structures of compounds will be determined including stereoconfiguration.The anti-viral bioactivity of new compounds including anti influenza A(H1N1) activities and anti-HBV activites will be conductied. Through activity evaluation, bioactive lead compounds are looking forward to be found and developed for the future drug research. These studies in this subject will provide structurally novel candidate compounds for anti-virus drug research and develope innovative drugs producing microorganism (resources),and these studies will contribute to investigation on the regulation of microbial metabolites with hydrogen ion.

流感，乙型肝炎等病毒性疾病一直以来都是严重危害人类健康的高发疾病。而针对病毒性疾病的药物，因种类少，毒副作用大，容易耐药等问题而备受药物研究人员的关注。项目拟在前期工作的基础上，继续运用抗流感和抗乙肝病毒体外筛选模型，对红树林的耐酸微生物的代谢产物展开研究。运用现代色谱技术跟踪分离活性化合物，运用现代光谱技术结合化学方法确定活性化合物的化学结构（包括立体结构）；应用流感病毒感染狗肾上皮细胞及乙肝病毒转染人肝癌细胞两种体外模型，评价单体化合物对流感及乙肝病毒的抑制和灭活作用，获得具有抗病毒活性的新化合物。为抗病毒创新药物的研发提供结构新颖的候选化合物及其产生菌（资源），研究工作将为探讨氢离子对微生物代谢产物调控的研究奠定基础。

病毒性疾病一直以来都是严重危害人类健康的高发疾病。而针对病毒性疾病的药物，因种类少，毒副作用大，容易耐药等问题而备受药物研究人员的关注。项目在前期工作的基础上，运用抗流感和抗乙肝病毒体外筛选模型，对红树林来源耐酸微生物的代谢产物展开研究。运用现代色谱技术跟踪分离活性化合物，运用现代光谱技术确定活性化合物的化学结构（包括立体结构）；应用流感病毒感染狗肾上皮细胞及乙肝病毒转染人肝癌细胞两种体外模型，评价单体化合物对流感及乙肝病毒的抑制作用。项目共采集红树林自然保护区红树林植物酸性根泥样品共计24份，从中分离获得耐酸微生物共计201株，包括耐酸真菌125株，耐酸放线菌76株。通过抗甲型流感病毒H1N1及抗乙肝病毒活性筛选，获得具有抗病毒活性菌株13株。对7株潜力菌株，进行了发酵优化，通过现代色谱及波谱学的联合应用，共获得单体化合物59个，其中新化合物9个。通过抗病毒活性筛选发现，11个化合物显示出了抗流感病毒活性，有3个与阳性药活性相当的，9个化合物显示出了低毒高效的抗乙肝病毒活性，其中1个新化合物具有成为抗乙肝病毒先导化合物的潜力。项目初步探讨了耐酸真菌的酸性调节机制。相关研究内容发表SCI论文8篇，核心期刊2篇，项目为抗病毒创新药物的研发提供结构新颖的候选化合物及其产生菌（资源），并为探讨氢离子对微生物代谢产物调控的生物学研究奠定基础。