SYNTHETIC PEPTIDE LIBRARIES FOR ANTIVIRAL DRUG DISCOVERY

感染1型和2型单纯疱疹病毒是主要的 美国的健康问题，每年新增病例超过50万例。新的 治疗疱疹病毒感染的药物是必要的，特别是在病毒 已知对核苷类似物产生抗药性。多肽一直是 被证明可以阻止病毒进入宿主细胞，其活性 重要的病毒编码酶和潜在的其他过程 病毒的生命周期。合成肽组合文库(SPCL) 将筛选由5200多万个D-氨基酸组成的六肽 针对单纯疱疹病毒1型的抗病毒活性。这个独一无二的 药物发现方法利用迭代选择过程来 确定单独定义的多肽，以进行进一步的疗效研究。什么时候 对D-氨基酸六肽文库的400个样本进行了筛选，22% 的混合物被发现是活性的。初步实验已经 揭示了D-氨基酸多肽混合物对病毒的抑制作用 宿主细胞的感染。D-氨基酸肽有望抵抗 更有效地降解蛋白质，因此具有更大的 作为局部有效的抗病毒治疗药物在体内的疗效。

Infections with herpes simplex viruses type-1 and type-2 are a major health problem in the U.S. with over 500,000 new cases per year. New drugs to treat herpes infections are needed, particularly since the virus is known to develop resistance to nucleoside analogs. Peptides have been shown to block the entry of viruses into the host cell, the activity of essential viral encoded enzymes and potentially other processes in the life cycle of viruses. A Synthetic Peptide Combinatorial Library (SPCL) composed of over 52 million D-amino acid hexapeptides will be screened for antiviral activity against herpes simples virus type-1. This unique drug discovery approach utilizes an iterative selection process to identify individual defined peptides for further efficacy studies. When the 400 samples of a D-amino acid hexapeptide library were screened, 22% of the mixtures were found to be active. Preliminary experiments have revealed D-amino acid peptide mixtures which inhibit the virus after infection of the host cell. D-amino acid peptides are expected to resist proteolytic degradation more effectively and therefore to have greater efficacy in vivo as topically active antiviral therapeutic agents.