De Novo Design of Envelope-Targeting Antiviral Peptide Drugs

该提案旨在开发新的基于肽的抗病毒药物，靶向病毒包膜，这是病毒感染所必需的脆弱结构。目标是设计选择性靶向病毒包膜而不影响宿主细胞膜的肽，同时还表现出对包膜病毒的高效力和对哺乳动物细胞的低细胞毒性。该提案采用了一种创新的方法，将进化算法与高通量分子动力学模拟相结合，以优化肽序列，并从病毒感染性和脂质体染料泄漏测定中获得反馈。最终目标是开发广谱抗病毒肽药物，可以对抗各种病毒病原体，包括新出现和重新出现的病毒。

The proposal aims to develop novel peptide-based antiviral drugs that target the viral envelope, which is a vulnerable structure necessary for viral infection. The goal is to design peptides that selectively target the viral envelope without affecting host cell membranes, while also exhibiting high potency against enveloped viruses and low cytotoxicity against mammalian cells. The proposal employs an innovative approach that combines evolutionary algorithms with high-throughput molecular dynamics simulations to optimize peptide sequences with feedback from viral infectivity and liposome dye leakage assays. The ultimate objective is to develop broad-spectrum antiviral peptide drugs that can combat a wide range of viral pathogens, including emerging and re-emerging viruses.