When organoids meet coronaviruses

Researchers from the group of Hans Clevers in collaboration with the group of Bart Haagmans (Erasmus MC) established an organoid biobank to search for the genes that are essential for the spreading of a SARS-CoV2 infection. Organoids are tiny 3D structures grown from stem cells that mimic organ function.

To find out more about the host factors that are specifically important for the replication and spreading of coronaviruses, the groups of Hans Clevers and Bart Haagmans developed a biobank of mutant intestinal organoids. This means that the organoids, that mimic the biology of the intestine, contained various mutations in the host factors that were previously discovered to be relevant for coronaviruses. These mutations cause changes in the activity of the host factors.

Consequently, the researchers injected the mutant organoids with SARS-CoV-2 – the virus responsible for COVID-19 – to study the effect of the mutations on the replication and spreading of the virus. Among other things, they identified the gene TMPRSS2 to be involved in this process: organoids with non-functioning TMPRSS2 showed reduced replication and spreading of the virus. This gene may therefore be an attractive therapeutic target for this coronavirus. Specific inhibitors for TMPRSS2 have recently been developed.