“Chikungunya virus (CHIKV), an emerging arbovirus of the family Togaviridae, causes Chikungunya fever (CHIKF), characterized by excessive inflammation and chronic arthralgia. Macrophages act as viral targets and amplifiers of inflammation, underscoring their crucial role in the pathogenesis of viral infections. Currently, no effective treatment exists for CHIKF, highlighting the need for novel therapeutic approaches.
Cannabinoids, known for their immunomodulatory and antiviral properties, have emerged as potential candidates. Here, we investigated the effects of cannabidiol (CBD) and WIN 55,212-2 (WIN) in CHIKV-infected human monocyte-derived macrophages (MDMs). Pre- and post-treatment efficacy were assessed at 6- and 24-h post-infection (h.p.i).
WIN, but not CBD, significantly reduced CHIKV replication in post-treatment assays, with effects most evident at 24 h.p.i. This antiviral activity occurred without significant changes in mRNA levels of IFNβ1, IFNλ1, and IL27p28, indicating that it did not alter the expression of type I/III interferons. Furthermore, WIN treatment reduced APOBEC3A mRNA levels. Additionally, WIN significantly reduced the production of CCL-2, as well as pro- (IL-6, TNF-α) and anti-inflammatory (IL-10) cytokines, while upregulating IRE1α and sXBP1 transcripts, suggesting modulation of ER stress pathways.
Overall, these findings identify WIN as a potential modulator of CHIKV replication and macrophage inflammatory response, acting through host-direct mechanisms that warrant further investigation.”
https://pubmed.ncbi.nlm.nih.gov/41197267/
“WIN 55,212-2 post-treatment reduced CHIKV replication and inflammation in MDMs by downregulating proinflammatory cytokines and chemokines and inducing ER stress via the PERK–IRE1α/sXBP1 pathway (Fig. 7B). Inhibiting these pathways partially restored viral load, suggesting their involvement in the antiviral effect. WIN 55,212-2 also decreased CHIKV nsP2 mRNA levels, without direct virucidal activity. These findings indicate that WIN functions as a dual-agent, both antiviral and immunomodulatory,”
https://www.sciencedirect.com/science/article/abs/pii/S1567576925017825?via%3Dihub
“WIN 55,212-2 is a synthetic cannabinoid and a potent full agonist of the cannabinoid receptors CB1 and CB2. Though it mimics the effects of tetrahydrocannabinol (THC), the compound has a distinctly different chemical structure. It has been extensively studied for its potential therapeutic effects due to its anti-inflammatory, analgesic, and neuroprotective properties. The compound is illegal in some countries, including the United States, where it is classified as a Schedule I controlled substance.”