Cell culture adaptation of SARS-CoV-2 is prevented on human airway cells with an active serine protease-mediated entry pathway, allowing the production of genetically stable virus stocks for laboratory experiments.
Whereas SARS-CoV-2 utilizes cathepsins to enter most cell lines, human airway organoids revealed that entry into relevant cells is dependent on serine proteases, which can be targeted for treatment.
Only three Spike mutations enable murine SARS-CoV-2 infection, which is still strictly ACE2 dependent and causes a COVID-19-like disease in mice with immunopathology-driven lung damage.
When culturing SARS-CoV-2 in the laboratory it is vital to avoid deletions in the gene for the spike protein that could affect the interpretation of experiments.
