Genc, D.Kati, A.Mandal, A.K.Ghorai, S.Salami, H.ElHefnawi, S.N.K.Altuntaş, S.2025-11-152025-11-15202597898152387099789815238693https://doi.org/10.2174/9789815238693125010008https://hdl.handle.net/20.500.12469/7599To date, no known drug therapy is available for COVID-19. Further, the complicated vaccination processes like limited infrastructure, insufficient know-how, and regulatory restrictions on vaccines caused this pandemic episode more badly. Due to the lack of ready-to-use vaccination, millions of people have been severely infected by SARS-CoV-2. Additionally, the increasing contagion risk of the SARS-CoV-2 variants makes drug repurposing studies more critical. Conventionally, antiviral drug repurposing has been conducted on two-dimensional (2D) cell culture systems or in vivo-based experimental setups. Recently, In vitro three-dimensional (3D) cell culture techniques have proven more coherent in mimicking host-pathogen interactions and exploring or repurposing drugs than other 2D cell culture methods. 3D culture techniques like organoids, bioprinting, and microfluidics/organ-on-a-chip have just been started to mimic the natural microenvironment respiratory system infected with SARS-CoV-2. These techniques avoid the need for animals in agreement with the 3R principles (Replacement, Reduction, and Refinement) to enhance animal welfare. Herein, SARS-CoV-2-host interaction and 3D cell culture techniques have been. © 2025 Elsevier B.V., All rights reserved.eninfo:eu-repo/semantics/closedAccessAlveolar TissueAntiviralDrug RepurposingDrug ScreeningDrug ScreeningInfectionSars-Cov-2, 3D Cell Culture ModelBook Part10.2174/97898152386931250100082-s2.0-105019631433