01585nas a2200241   4500000000100000000000100001008004100002260001200043100002400055700001700079700002300096700001400119700002800133700001200161700001600173700002400189245006600213856004800279300001100327490000700338520098400345022001401329       2023                            d  c2023-021 aFahimeh Shahabipour1 aSandro Satta1 aMahboobeh Mahmoodi1 aArgus Sun1 aNatan Roberto de Barros1 aSong Li1 aTzung Hsiai1 aNureddin Ashammakhi00aEngineering organ-on-a-chip systems to model viral infections  uhttps://dx.doi.org/10.1088/1758-5090/ac6538  a0220010 v153 aInfectious diseases remain a public healthcare concern worldwide. Amidst the pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 infection, increasing resources have been diverted to investigate therapeutics targeting the COVID-19 spike glycoprotein and to develop various classes of vaccines. Most of the current investigations employ two-dimensional (2D) cell culture and animal models. However, 2D culture negates the multicellular interactions and three-dimensional (3D) microenvironment, and animal models cannot mimic human physiology because of interspecies differences. On the other hand, organ-on-a-chip (OoC) devices introduce a game-changer to model viral infections in human tissues, facilitating high-throughput screening of antiviral therapeutics. In this context, this review provides an overview of the in vitro OoC-based modeling of viral infection, highlighting the strengths and challenges for the future.  a1758-5090