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


Journal

Alcohol, clinical & experimental research
ISSN: 2993-7175
Titre abrégé: Alcohol Clin Exp Res (Hoboken)
Pays: United States
ID NLM: 9918609780906676

Informations de publication

Date de publication:
01 2023
Historique:
revised: 01 11 2022
received: 30 08 2022
accepted: 06 11 2022
pubmed: 11 11 2022
medline: 25 2 2023
entrez: 10 11 2022
Statut: ppublish

Résumé

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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 36352814
doi: 10.1111/acer.14974
pmc: PMC9878066
doi:

Substances chimiques

Acetaldehyde GO1N1ZPR3B
spike protein, SARS-CoV-2 0
Spike Glycoprotein, Coronavirus 0
Pulmonary Surfactant-Associated Protein D 0
Malondialdehyde 4Y8F71G49Q
Ethanol 3K9958V90M
Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

95-103

Subventions

Organisme : BLRD VA
ID : I01 BX005413
Pays : United States
Organisme : BLRD VA
ID : IK6 BX003781
Pays : United States

Informations de copyright

© 2022 Research Society on Alcohol.

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Auteurs

Abenaya Muralidharan (A)

Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Christopher Bauer (C)

Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Dawn M Katafiasz (DM)

Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Danielle Pham (D)

Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Opeoluwa O Oyewole (OO)

Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.

M Jane Morwitzer (MJ)

Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Enakshi Roy (E)

Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Kristina L Bailey (KL)

Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA.

St Patrick Reid (SP)

Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Todd A Wyatt (TA)

Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA.
Department of Environmental, Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska, USA.

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