Prediction of SARS-CoV interaction with host proteins during lung aging reveals a potential role for TRIB3 in COVID-19

Diogo de Moraes; Brunno Vivone Buquete Paiva; Sarah Santiloni Cury; João Pessoa Araújo Junior; Marcelo Alves da Silva Mori; Robson Francisco Carvalho

The reanalysis of lung single-cell RNA sequencing data 19, 20 demonstrated TRIB3 expressed mainly in alveolar type I (AT1) and type II (AT2) cells and in ciliated cells (Figure 1d -f, Figure S3 ), which also express SARS-CoV-2 receptor ACE2 7, 8, 21 . The involvement of TRIB3 in viral infection is poorly understood; however, its inhibition was associated with an increase of hepatitis C virus (HCV) replication 22 . Additionally, TRIB3 negatively regulates the entry step of the HCV life cycle and propagation 22 Table S8 ). We found that genes that decrease their expression with aging and genes that are up-regulated with SARS-CoV infections generated the most significant network, with overrepresented genes associated with mitotic cell cycle and surfactant metabolism ( Figure 2 ). The decreased capacity of cellular division on aging is associated with cellular senescence -a mechanism that stops cells with damaged DNA from replicating 26 -and progenitor cell exhaustion 27 . The altered metabolism or secretion of surfactants by AT2 cells reduces the ability of the lungs to expand and increases the risk of lung collapse in HCoVs infections 28, 29 . Moreover, Sftpc -/-(Surfactant Protein C) mice have worse viral infections than controls 30 , and its human homolog decreased with aging while it is up-regulated on SARS-CoV infections ( Figure 2 ). Thus, the pneumonia-like lung injury found on severe cases of COVID-19 infections 5,6 may be aggravated by impaired lung regeneration and altered metabolism of surfactants in older male patients.