Bioinformatic analysis of SMN1-ACE/ACE2 interactions hinted at a potential protective effect of spinal muscular atrophy against COVID-19-induced lung injury

Brief Bioinform. 2021 Mar 22;22(2):1291-1296. doi: 10.1093/bib/bbaa285.

Abstract

Patients with spinal muscular atrophy (SMA) are susceptible to the respiratory infections and might be at a heightened risk of poor clinical outcomes upon contracting coronavirus disease 2019 (COVID-19). In the face of the COVID-19 pandemic, the potential associations of SMA with the susceptibility to and prognostication of COVID-19 need to be clarified. We documented an SMA case who contracted COVID-19 but only developed mild-to-moderate clinical and radiological manifestations of pneumonia, which were relieved by a combined antiviral and supportive treatment. We then reviewed a cohort of patients with SMA who had been living in the Hubei province since November 2019, among which the only 1 out of 56 was diagnosed with COVID-19 (1.79%, 1/56). Bioinformatic analysis was carried out to delineate the potential genetic crosstalk between SMN1 (mutation of which leads to SMA) and COVID-19/lung injury-associated pathways. Protein-protein interaction analysis by STRING suggested that loss-of-function of SMN1 might modulate COVID-19 pathogenesis through CFTR, CXCL8, TNF and ACE. Expression quantitative trait loci analysis also revealed a link between SMN1 and ACE2, despite low-confidence protein-protein interactions as suggested by STRING. This bioinformatic analysis could give hint on why SMA might not necessarily lead to poor outcomes in patients with COVID-19.

Keywords: ACE2; COVID-19; SMN1; spinal muscular atrophy.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / metabolism*
  • COVID-19 / metabolism*
  • COVID-19 / virology
  • Disease Susceptibility
  • Humans
  • Muscular Atrophy, Spinal / complications*
  • Muscular Atrophy, Spinal / metabolism
  • Muscular Atrophy, Spinal / prevention & control
  • Protein Binding
  • Protein Interaction Maps
  • Renin-Angiotensin System
  • SARS-CoV-2 / isolation & purification
  • Signal Transduction
  • Survival of Motor Neuron 1 Protein / genetics
  • Survival of Motor Neuron 1 Protein / metabolism*

Substances

  • SMN1 protein, human
  • Survival of Motor Neuron 1 Protein
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2