ORCID

0000-0003-0184-8196 (Nagre)

Document Type

Article

Publication Date

2026

DOI

10.1007/s00408-026-00870-6

Publication Title

Lung

Volume

204

Issue

1

Pages

7

Abstract

Introduction

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to pose major health challenges despite effective vaccination efforts. The sustained occurrence of breakthrough infections and emerging variants of the virus highlights the need for additional therapeutic strategies. Given the anti-inflammatory role of the cannabinoid type 2 receptor (CB2R), we examined the effect of CB2R activation in SARS-CoV-2 spike protein subunit 1 (S1SP)-induced acute lung injury (ALI).

Methods

ALI was induced in mice by intratracheal (i.t.) administration of S1SP, followed by treatment with the CB2R agonist HU308 (5 mg/kg, intraperitoneal: i.p.) 1 h post-S1SP and every 24 h thereafter. Lung function, bronchoalveolar lavage fluid (BALF) parameters, cytokine levels, and inflammatory signaling were assessed at 48 h following S1SP exposure.

Results

HU308 treatment significantly reduced S1SP-induced pulmonary dysfunction, immune cell infiltration, neutrophil activation, and proinflammatory cytokine production, while suppressing NF-κB and STAT3 activation. HU308 treatment restored the Nrf2 expression in the lung.

Conclusion

CB2R activation ameliorates S1SP-induced lung inflammation and injury, suggesting its therapeutic potential against COVID-19-related ALI.

Rights

© 2026 The Authors.

This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. 

Data Availability

Article states: "Data supporting the findings of this study are available from the corresponding author upon request."

Original Publication Citation

Lockett, J., Nicholson, G., Richards, N., Washington, R., & Nagre, N. (2026). HU308, a selective cannabinoid type-2 receptor agonist, mitigates SARS-CoV-2 spike protein-induced acute lung injury in mice. Lung, 204(1), Article 7. https://doi.org/10.1007/s00408-026-00870-6

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