The Nucleocapsid Protein of SARS-CoV-2 Abolished Pluripotency in Human Induced Pluripotent Stem Cells

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is raging across the world, leading to a mortality rate of 3.4%. As a potential vaccine and therapeutic target, the nucleocapsid protein of SARS-CoV-2 (nCoVN) functions in packaging the viral genome and viral self-assembly. To investigate the biological effect of nCoVN to human induced pluripotent stem cells (iPSC), genetically engineered iPSC overexpressing nCoVN (iPSC-nCoVN) were generated by lentiviral expression systems. Unexpectedly, the morphology and proliferation rate of iPSC were changed after nCoVN expressing for two weeks. The pluripotency markers SSEA4 and TRA-1-81 were not detectable in iPSC-nCoVN. Meanwhile, iPSC-nCoVN lost the ability for differentiation into cardiomyocytes when using a routine differentiation protocol. Our data suggested that nCoVN disrupted the pluripotent properties of iPSC and turned them into fibroblasts, which provided a new insight to the pathogenic mechanism of SARS-CoV-2.