As the COVID-19 outbreak continues to affect thousands of people worldwide, there is an urgent need to develop strategies that lead to effective treatments. Although vaccination has contributed to attenuating severe symptoms, there is a need for specific drugs to address the effects of SARS-CoV-2 infection on different body systems. Conventional drug development includes highly time-consuming and expensive processes; thus, new technologies must accelerate drug discovery. 1
Traditional 2D cell culture does not accurately capture the effects of a physiologically relevant environment, failing to promote appropriate cell-cell and cell-environment interactions, which contributes to the high failure rate in drug development. 3D cell culture models can bridge the gap between conventional cell culture and in vivo models, further clarifying pathogen-host cell interactions.23
Figure 1: Strategies to produce 3D in vitro models for studying SARS-CoV-2 infection of different organs and tissues. 4
Organoids have been used to mimic various tissues, such as the brain, lung, and liver, to study different virus-host interactions. In most cases, the results showed that organoids simulated the native tissues morphologically and functionally.4 Monteil et al. used iPSCs to produce human capillary and renal organoids to assess the infectivity of SARS-CoV-2. Respiratory symptoms are the clinical predominance of patients with COVID-19, but as SARS-CoV-2 has already been identified in the urine of patients, it can be assumed that the virus spreads from the lungs to the kidneys through the vasculature.5
Angiotensin-converting enzyme 2 (ACE2) is the critical coronavirus receptor of SARS-CoV and has been indicated as a lung protector against injury, providing a molecular explanation for severe lung failure and death due to SARS-CoV infections. The study by Monteil et al. showed that the entry of SARS-CoV-2 into organoids was significantly reduced by clinical grade human recombinant soluble ACE2 in the early stages of the disease. 5
Figure 2: Inhibition of SARS-CoV-2 Infections in engineered human tissues using clinical grade soluble human ACE2. 5
Recently, Wang et al. established 3D human gastric organoids as a working model for the study of the mechanism of primary infection of SARS-CoV-2 in the gastrointestinal tract. The enteric infection model system developed in the study can act as a platform to screen targeted therapeutics for virus variants based on infectivity and host susceptibility.6
The use of 3D models makes possible the assessment of drugs for the treatment of SARS-CoV-2-infected patients using their own cells, which can help the development of a rational design of targeted therapeutics for more effective and personalized treatments.