Frontiers in Immunology (Mar 2024)

Human surfactant protein A inhibits SARS-CoV-2 infectivity and alleviates lung injury in a mouse infection model

  • Ikechukwu B. Jacob,
  • Ikechukwu B. Jacob,
  • Amanda Gemmiti,
  • Weichuan Xiong,
  • Erin Reynolds,
  • Brian Nicholas,
  • Saravanan Thangamani,
  • Hongpeng Jia,
  • Guirong Wang,
  • Guirong Wang

DOI
https://doi.org/10.3389/fimmu.2024.1370511
Journal volume & issue
Vol. 15

Abstract

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IntroductionSARS coronavirus 2 (SARS-CoV-2) infects human angiotensin-converting enzyme 2 (hACE2)-expressing lung epithelial cells through its spike (S) protein. The S protein is highly glycosylated and could be a target for lectins. Surfactant protein A (SP-A) is a collagen-containing C-type lectin, expressed by mucosal epithelial cells and mediates its antiviral activities by binding to viral glycoproteins.ObjectiveThis study examined the mechanistic role of human SP-A in SARS-CoV-2 infectivity and lung injury in vitro and in vivo.ResultsHuman SP-A can bind both SARS-CoV-2 S protein and hACE2 in a dose-dependent manner (p<0.01). Pre-incubation of SARS-CoV-2 (Delta) with human SP-A inhibited virus binding and entry and reduced viral load in human lung epithelial cells, evidenced by the dose-dependent decrease in viral RNA, nucleocapsid protein (NP), and titer (p<0.01). We observed significant weight loss, increased viral burden, and mortality rate, and more severe lung injury in SARS-CoV-2 infected hACE2/SP-A KO mice (SP-A deficient mice with hACE2 transgene) compared to infected hACE2/mSP-A (K18) and hACE2/hSP-A1 (6A2) mice (with both hACE2 and human SP-A1 transgenes) 6 Days Post-infection (DPI). Furthermore, increased SP-A level was observed in the saliva of COVID-19 patients compared to healthy controls (p<0.05), but severe COVID-19 patients had relatively lower SP-A levels than moderate COVID-19 patients (p<0.05).DiscussionCollectively, human SP-A attenuates SARS-CoV-2-induced acute lung injury (ALI) by directly binding to the S protein and hACE2, and inhibiting its infectivity; and SP-A level in the saliva of COVID-19 patients might serve as a biomarker for COVID-19 severity.

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