Costunolide as a Conceptual Framework for Host-Directed Antiviral Modulation: Mechanistic Insights and Future Perspectives

Leonardo Acuña¹, Mariam Ahumada Sabagh², Víctor David Osorio Castillo^1,2, Caverly Gooden³, María Luisa Veisaga⁴, Juan Liuzzi^5,6, Manuel A. Barbieri^2,3,5,6,7,*
1 Ph.D. Biochemistry Program, Florida International University, Miami, FL, USA
2 Department of Biological Sciences, Florida International University, Miami, FL, USA
3 Graduate Certificate in Molecular and Biomedical Sciences, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
4 Women’s Studies Department, Florida International University, Miami, FL, USA
5 Department of Dietetics and Nutrition, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL, USA
6 Biomedical Science Institute, Florida International University, Miami, FL, USA
7 International Center of Tropical Botany, Florida International University, Miami, FL, USA
* Corresponding Author: Manuel A. Barbieri. Email: email
(This article belongs to the Special Issue: Bioactive Natural Components as Regulators of Cellular Pathways and Disease Progression)

BIOCELL https://doi.org/10.32604/biocell.2026.079670

Received 26 January 2026; Accepted 07 May 2026; Published online 01 June 2026

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Abstract

Costunolide, a sesquiterpene lactone from Saussurea lappa Clarke, exhibits broad pharmacological properties, including anti-inflammatory and anticancer effects. This review examines its emerging potential as a host-directed antiviral compound. Costunolide modulates conserved host signaling pathways frequently exploited during viral infection, including nuclear factor-kappa B (NF-κB), the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, and mitogen-activated protein kinase (MAPK) cascades. Inhibition of NF-κB may suppress viral transcription in human immunodeficiency virus (HIV-1) infection, while NLRP3 blockade may limit inflammasome-driven viral reactivation in Epstein–Barr virus (EBV) infection and attenuate hyperinflammation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease. Additional modulation of phosphoinositide 3-kinase/AKT (PI3K/AKT), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and Wnt/β-catenin pathways further expands its host-directed antiviral profile. These pleiotropic effects are mechanistically linked to the electrophilic α-methylene-γ-lactone moiety, which undergoes cysteine-directed Michael addition on target proteins. Collectively, these findings position costunolide as a promising host-directed antiviral scaffold, though pharmacokinetic optimization and virus-specific experimental validation remain necessary prerequisites for therapeutic translation.

Keywords

Costunolide; antiviral activity; nuclear factor-kappa B pathway; NOD-like receptor family pyrin domain-containing 3 inflammasome; mitogen-activated protein kinase signaling; viral replication

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Costunolide as a Conceptual Framework for Host-Directed Antiviral Modulation: Mechanistic Insights and Future Perspectives

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