02513nas a2200493 4500000000100000008004100001260001500042653002000057653001800077653002700095653001400122653002000136653001900156653002600175653001500201653001200216653001300228100001200241700001600253700001500269700001400284700002800298700001700326700001400343700001500357700001700372700001500389700001300404700001200417700001500429700001200444700001700456700001100473700001700484700001500501700001500516700001600531245008900547856007200636300001100708490000600719520128000725022001402005 2023 d c2023-12-0110aAntiviral drugs10aGut-on-a-chip10aHuman organs-on-a-chip10aInfluenza10aLiver-on-a-Chip10alung-on-a-chip10aLymph nodes-on-a-chip10aSARS-CoV-210avaccine10aVirology1 aJing Li1 aHaiqing Bai1 aZihao Wang1 aBeibei Xu1 aKristen N. Peters Olson1 aChengyao Liu1 aYinlei Su1 aJiawei Hao1 aJinying Shen1 aXuetong Xi1 aJie Zhen1 aRong Yu1 aYacong Sun1 aXin Xie1 aWen-xia Tian1 aFei Yu1 aXiaoheng Liu1 aLihe Zhang1 aDemin Zhou1 aLonglong Si00aAdvancements in organs-on-chips technology for viral disease and anti-viral research uhttps://www.sciencedirect.com/science/article/pii/S2666102023000058 a1000300 v53 aDisease models that can accurately recapitulate human pathophysiology during infection and clinical response to antiviral therapeutics are still lacking, which represents a major barrier in drug development. The emergence of human Organs-on-a-Chip that integrated microfluidics with three-dimensional (3D) cell culture, may become the potential solution for this urgent need. Human Organs-on-a-Chip aims to recapitulate human pathophysiology by incorporating tissue-relevant cell types and their microenvironment, such as dynamic fluid flow, mechanical cues, tissue–tissue interfaces, and immune cells to increase the predictive validity of in vitro experimental models. Human Organs-on-a-Chip has a broad range of potential applications in basic biomedical research, preclinical drug development, and personalized medicine. This review focuses on its use in the fields of virology and infectious diseases. We reviewed various types of human Organs-on-a-Chip-based viral infection models and their application in studying viral life cycle, pathogenesis, virus-host interaction, and drug responses to virus- and host-targeted therapies. We conclude by proposing challenges and future research avenues for leveraging this promising technology to prepare for future pandemics. a2666-1020