Gu Xiaoxia, Zheng Mengzhu, Gao Ya, Lin Shuang, Zhang Xiaotian, Chen Chunmei, Zhu Hucheng, Sun Weiguang, Zhang Yonghui
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
Acta Pharm Sin B. 2025 Apr;15(4):1723-1751. doi: 10.1016/j.apsb.2025.03.011. Epub 2025 Mar 8.
Viruses constitute a significant group of pathogens that have caused numerous fatalities and substantial economic losses in recent years, particularly with the emergence of coronaviruses. While the impact of SARS-CoV-2 appears to be diminishing in daily life, only a limited number of drugs have received approval or emergency use authorization for its treatment. Given the high mutation rate of viral genomes, host-directed agents (HDAs) have emerged as a preferred choice due to their broad applicability and lasting effectiveness. In contrast to direct-acting antivirals (DAAs), HDAs offer several advantages, including broad-spectrum antiviral activities, potential efficacy against future emerging viruses, and a lower likelihood of inducing drug resistance. In our review article, we have synthesized known host-directed antiviral targets that span diverse cellular pathways and mechanisms, shedding light on the intricate interplay between host cells and viruses. Additionally, we have provided a brief overview of the development of HDAs based on these targets. We aim for this comprehensive analysis to offer valuable perspectives and insights that can guide future antiviral research and drug development efforts.
病毒是一类重要的病原体,近年来已导致无数人死亡和巨大的经济损失,尤其是随着冠状病毒的出现。虽然严重急性呼吸综合征冠状病毒2(SARS-CoV-2)在日常生活中的影响似乎正在减弱,但只有少数药物已获得其治疗的批准或紧急使用授权。鉴于病毒基因组的高突变率,宿主导向药物(HDA)因其广泛的适用性和持久的有效性而成为首选。与直接作用抗病毒药物(DAA)相比,HDA具有多种优势,包括广谱抗病毒活性、对未来新兴病毒的潜在疗效以及诱导耐药性的可能性较低。在我们的综述文章中,我们综合了已知的宿主导向抗病毒靶点,这些靶点跨越了不同的细胞途径和机制,揭示了宿主细胞与病毒之间复杂的相互作用。此外,我们还基于这些靶点对HDA的开发进行了简要概述。我们希望这种全面分析能够提供有价值的观点和见解,以指导未来的抗病毒研究和药物开发工作。