Prediction of SARS-CoV Interaction with Host Proteins during Lung Aging Reveals a Potential Role for TRIB3 in COVID-19

Autor(es)

de Moraes, Diogo ^[1] ; Buquete Paiva, Brunno Vivone ^{[1, 2]} ; Cury, Sarah Santiloni ^[1] ; Araujo Junior, Joao Pessoa ^[3] ; da Silva Mori, Marcelo Alves ^[4] ; Carvalho, Robson Francisco ^[1] ; Ludwig, Raissa Guimaraes ^[4]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Inst Biosci, Dept Struct & Funct Biol, Botucatu, SP - Brazil

^[2] Sao Paulo State Univ, Fac Med, UNESP, Botucatu, SP - Brazil

^[3] Sao Paulo State Univ UNESP, Inst Biosci, Dept Chem & Biol Sci, Botucatu, SP - Brazil

^[4] State Univ Campinas UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Aging and disease; v. 12, n. 1, p. 42-49, FEB 1 2021.
• Citações Web of Science: 0

Resumo

COVID-19 is prevalent in the elderly. Old individuals are more likely to develop pneumonia and respiratory failure due to alveolar damage, suggesting that lung senescence may increase the susceptibility to SARS-CoV-2 infection and replication. Considering that human coronavirus (HCoVs; SARS-CoV-2 and SARS-CoV) require host cellular factors for infection and replication, we analyzed Genotype-Tissue Expression (GTEx) data to test whether lung aging is associated with transcriptional changes in human protein-coding genes that potentially interact with these viruses. We found decreased expression of the gene tribbles homolog 3 (TRIB3) during aging in male individuals, and its protein was predicted to interact with HCoVs nucleocapsid protein and RNA-dependent RNA polymerase. Using publicly available lung single-cell data, we found TRIB3 expressed mainly in alveolar epithelial cells that express SARS-CoV-2 receptor ACE2. Functional enrichment analysis of age-related genes, in common with SARS-CoV-induced perturbations, revealed genes associated with the mitotic cell cycle and surfactant metabolism. Given that TRIB3 was previously reported to decrease virus infection and replication, the decreased expression of TRIB3 in aged lungs may help explain why older male patients are related to more severe cases of the COVID-19. Thus, drugs that stimulate TRIB3 expression should be evaluated as a potential therapy for the disease. (AU)

• Processo FAPESP: 17/01184-9 - CAMeLEOm: análise entre espécies dos efeitos metabólicos, na expectativa de vida e ômicas de miméticos de restrição dietética
• Beneficiário: Marcelo Alves da Silva Mori
• Modalidade de apoio: Auxílio à Pesquisa - Temático