In Vitro Virology

核心C：病毒学将通过提供以下服务支持研究项目I、II和III以及核心B和D： 特异性试剂、抗病毒和其它抗感染评价，以及嘧啶二酮类的功效数据， ISIS 5320寡核苷酸和单独的NCp 7病毒灭活剂和组合产品。核心C将 通过实现以下目标来实现这些目标： 目的1：主要抗病毒疗效和毒性试验：将利用抗病毒疗效和毒性数据 全病毒复制测定和特异性细胞和生物化学测定，以测量 活性杀微生物剂和基于其确定的作用机制配制的产品。毒性 对于每种抗病毒测量，将平行进行评价。目标2：评价 复方杀微生物剂产品的活性：本目标旨在利用体外标准品 杀微生物剂效力测定，以评估、量化和优先考虑将被 作为长效杀微生物剂开发，用于在离体宫颈外植体模型中进行评估，以及进一步 开发成凝胶和环状产品。目的3：评价阴道和精液的作用 关于病毒活性和杀微生物剂效力和毒性：我们将进行体外效力和毒性研究 使用精浆和阴道液添加剂对所进行的每种抗病毒测定进行评价， 进一步确定这些液体在病毒感染性、杀微生物剂作用和细胞方面的生物学特性， 目的4：开发抗微生物剂病毒株和评价抗微生物剂的能力。 抑制野生型和抗性病毒传播的杀微生物剂：我们将选择 对单独的每种杀微生物剂和彼此组合的每种杀微生物剂的抗性，并评估 目标5：毒性 杀微生物剂产品和配方材料的评价：将进行基于细胞的体外毒理学试验。 利用细胞系、相关乳杆菌属物种和离体组织进行。目的6：临床前 单独和混合的杀微生物剂产品的开发： 研究将评估其抗病毒潜力，与其临床试验进展一致。

Core C: Virology will support Research Projects I, II and III and Cores B and D through the provision of specific reagents, antiviral and other anti-infective evaluations, and efficacy data for the pyrimidinediones, ISIS 5320 oligonucleotide, and NCp7 viral inactivating agents alone and in combination products. Core C will accomplish these goals by implementation of the following objectives: Objective 1: Primary Antiviral Efficacy and Toxicity Testing: The antiviral efficacy and toxicity data will utilize whole virus replication assays and specific cellular and biochemical assays to measure the antiviral effects of the active microbicide and formulated product based on their defined mechanisms of action. Toxicity evaluations will be performed in parallel for each antiviral measurement. Objective 2: Evaluation of the Activity of Combination Microbicide Products: The aim of this objective is to utilize standard in vitro microbicide efficacy assays to evaluate, quantify and prioritize combinations of microbicide products to be developed as long-lasting microbicides for evaluation in ex vivo cervical explant models as well as for further development as gel and ring products. Objective 3: Evaluation of the Effects of Vaginal and Seminal Fluids on Viral Infectivity and Microbicide Efficacy and Toxicity: We will perform in vitro efficacy and toxicity evaluations using seminal plasma and vaginal fluid additives to each of the antiviral assays performed and to further define the biological properties of these fluids on viral infectivity, microbicide action, and cellular toxicity.Objective 4: Development of Microbicide-Resistant Virus Strains and Evaluation of the Ability of the Microbicides to Inhibit the Transmission of Wild Type and Resistant Virus: We will select for viruses that are resistant to each of the microbicides alone and in combination with one another and evaluate the ability of the microbicides to totally suppress the transmission of wild type and resistant viruses.Objective 5: Toxicity Evaluation of Microbicide Products and Formulated Materials: Cell-based in vitro toxicology testing will be performed utilizing cell lines, relevant Lactobacilli species, and ex vivo tissues. Objective 6: Preclinical Development of Microbicide Products Alone and In Combination: Lead microbicide products defined by the studies will be assessed for their antiviral potential consistent with their advancement to clinical testing.