02446nas a2200397   4500000000100000000000100001008004100002260001200043653002300055653002100078653001300099653002800112653002000140653003300160653001100193653001400204653001500218653002400233653002300257653002100280653001900301653002000320653002000340653001400360653003700374653001400411100002900425700002400454700002400478700002400502245012700526300001200653490000700665520136200672022001402034       2021                            d  c2021-0610a3D in vitro models10aAntiviral Agents10aCOVID-1910aCOVID-19 Drug Treatment10aCells, Cultured10aDrug Evaluation, Preclinical10aHumans10aorganoids10aSARS-CoV-210aSpheroids, Cellular10aTissue engineering10aTissue Scaffolds10aDrug screening10ahigh-throughput10aInfection model10aorganoids10ascaffold-free tissue engineering10aspheroids1 aGabriela S. Kronemberger1 aFabiana A. Carneiro1 aDanielle F. Rezende1 aLeandra S. Baptista00aSpheroids and organoids as humanized 3D scaffold-free engineered tissues for SARS-CoV-2 viral infection and drug screening  a548-5580 v453 aThe new coronavirus (2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was officially declared by the World Health Organization (WHO) as a pandemic in March 2020. To date, there are no specific antiviral drugs proven to be effective in treating SARS-CoV-2, requiring joint efforts from different research fronts to discover the best route of treatment. The first decisions in drug discovery are based on 2D cell culture using high-throughput screening. In this context, spheroids and organoids emerge as a reliable alternative. Both are scaffold-free 3D engineered constructs that recapitulate key cellular and molecular events of tissue physiology. Different studies have already shown their advantages as a model for different infectious diseases, including SARS-CoV-2 and for drug screening. The use of these 3D engineered tissues as an in vitro model can fill the gap between 2D cell culture and in vivo preclinical assays (animal models) as they could recapitulate the entire viral life cycle. The main objective of this review is to understand spheroid and organoid biology, highlighting their advantages and disadvantages, and how these scaffold-free engineered tissues can contribute to a better comprehension of viral infection by SARS-CoV-2 and to the development of in vitro high-throughput models for drug screening.  a1525-1594