Malondialdehyde acetaldehyde adduction of surfactant protein D attenuates SARS-CoV-2 spike protein binding and virus neutralization

Abenaya Muralidharan, Christopher Bauer, Dawn M. Katafiasz, Danielle Pham, Opeoluwa O. Oyewole, M. Jane Morwitzer, Enakshi Roy, Kristina L. Bailey, St Patrick Reid, Todd A. Wyatt

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Over 43% of the world's population regularly consumes alcohol. Although not commonly known, alcohol can have a significant impact on the respiratory environment. Living in the time of the COVID-19 pandemic, alcohol misuse can have a particularly deleterious effect on SARS-CoV-2-infected individuals and, in turn, the overall healthcare system. Patients with alcohol use disorders have higher odds of COVID-19-associated hospitalization and mortality. Even though the detrimental role of alcohol on COVID-19 outcomes has been established, the underlying mechanisms are yet to be fully understood. Alcohol misuse has been shown to induce oxidative damage in the lungs through the production of reactive aldehydes such as malondialdehyde and acetaldehyde (MAA). MAA can then form adducts with proteins, altering their structure and function. One such protein is surfactant protein D (SPD), which plays an important role in innate immunity against pathogens. Methods and Results: In this study, we examined whether MAA adduction of SPD (SPD-MAA) attenuates the ability of SPD to bind SARS-CoV-2 spike protein, reversing SPD-mediated virus neutralization. Using ELISA, we show that SPD-MAA is unable to competitively bind spike protein and prevent ACE2 receptor binding. Similarly, SPD-MAA fails to inhibit entry of wild-type SARS-CoV-2 virus into Calu-3 cells, a lung epithelial cell line, as well as ciliated primary human bronchial epithelial cells isolated from healthy individuals. Conclusions: Overall, MAA adduction of SPD, a consequence of alcohol overconsumption, represents one mechanism of compromised lung innate defense against SARS-CoV-2, highlighting a possible mechanism underlying COVID-19 severity and related mortality in patients who misuse alcohol.

Original languageEnglish (US)
Pages (from-to)95-103
Number of pages9
JournalAlcohol: Clinical and Experimental Research
Volume47
Issue number1
DOIs
StatePublished - Jan 2023

Keywords

  • SARS-CoV-2
  • alcohol
  • cigarette smoke
  • lung immunity
  • malondialdehyde acetaldehyde
  • surfactant protein D

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • General Medicine
  • Medicine (miscellaneous)
  • Toxicology

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