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J Cell Mol Med
. 2026 Jul;30(13):e71213.
doi: 10.1111/jcmm.71213.
Therapeutic Efficacy of Indole-3-Carbinol Against SARS-CoV-2-Induced Acute Respiratory Distress Syndrome: A Dual Antiviral and Anti-Inflammatory Approach in a Golden Syrian Hamster Model
Centofanti Federica 1 , Rizzacasa Barbara 2 , Latini Andrea 1 3 , Biancolella Michela 4 , Pocci Marco 5 , Servadei Francesca 6 , Scimeca Manuel 6 , Mauriello Alessandro 6 , Bernadett Palyi 7 , Daniel Deri 7 8 , Berenike Novak 7 , Zoltan Kis 7 8 , Claudia Filippone 8 9 , Pier Paolo Pandolfi 2 , Novelli Giuseppe 1
Affiliations
SARS-CoV-2 has caused a global pandemic, resulting in over two million deaths and creating an urgent need for effective treatments. Severe COVID-19 is frequently complicated by respiratory failure and acute respiratory distress syndrome (ARDS), the primary drivers of mortality. Indole-3-Carbinol (I3C), a natural compound derived from Brassicaceae that acts as an inhibitor of HECT family E3 ubiquitin ligases, exhibits potent anti-SARS-CoV-2 activity and inhibits viral egress. However, its in vivo therapeutic efficacy against SARS-CoV-2-induced lung injury remains unproven. We evaluated the therapeutic efficacy of I3C in reducing the severity of SARS-CoV-2 infection and associated lung lesions using the Syrian golden hamster (Mesocricetus auratus) model, which recapitulates the acute lung injury observed in human COVID-19. Treatment with a non-toxic dose of I3C (2 mg) significantly ameliorated disease across all parameters, reducing weight loss, improving clinical symptom scores and reducing histopathological lung damage observed post-mortem. A significant reduction in pulmonary TNF-α levels accompanied this. These findings indicate that I3C mitigates COVID-19-related morbidity at clinically relevant, non-toxic doses. Given its dual antiviral and anti-inflammatory mechanisms, I3C represents a compelling therapeutic candidate for further clinical investigation.
Keywords: HECT E3 ligase inhibition; SARS‐CoV‐2; hamster; indole‐3‐carbinol; preclinical study.
. 2026 Jul;30(13):e71213.
doi: 10.1111/jcmm.71213.
Therapeutic Efficacy of Indole-3-Carbinol Against SARS-CoV-2-Induced Acute Respiratory Distress Syndrome: A Dual Antiviral and Anti-Inflammatory Approach in a Golden Syrian Hamster Model
Centofanti Federica 1 , Rizzacasa Barbara 2 , Latini Andrea 1 3 , Biancolella Michela 4 , Pocci Marco 5 , Servadei Francesca 6 , Scimeca Manuel 6 , Mauriello Alessandro 6 , Bernadett Palyi 7 , Daniel Deri 7 8 , Berenike Novak 7 , Zoltan Kis 7 8 , Claudia Filippone 8 9 , Pier Paolo Pandolfi 2 , Novelli Giuseppe 1
Affiliations
- PMID: 42438898
- DOI: 10.1111/jcmm.71213
SARS-CoV-2 has caused a global pandemic, resulting in over two million deaths and creating an urgent need for effective treatments. Severe COVID-19 is frequently complicated by respiratory failure and acute respiratory distress syndrome (ARDS), the primary drivers of mortality. Indole-3-Carbinol (I3C), a natural compound derived from Brassicaceae that acts as an inhibitor of HECT family E3 ubiquitin ligases, exhibits potent anti-SARS-CoV-2 activity and inhibits viral egress. However, its in vivo therapeutic efficacy against SARS-CoV-2-induced lung injury remains unproven. We evaluated the therapeutic efficacy of I3C in reducing the severity of SARS-CoV-2 infection and associated lung lesions using the Syrian golden hamster (Mesocricetus auratus) model, which recapitulates the acute lung injury observed in human COVID-19. Treatment with a non-toxic dose of I3C (2 mg) significantly ameliorated disease across all parameters, reducing weight loss, improving clinical symptom scores and reducing histopathological lung damage observed post-mortem. A significant reduction in pulmonary TNF-α levels accompanied this. These findings indicate that I3C mitigates COVID-19-related morbidity at clinically relevant, non-toxic doses. Given its dual antiviral and anti-inflammatory mechanisms, I3C represents a compelling therapeutic candidate for further clinical investigation.
Keywords: HECT E3 ligase inhibition; SARS‐CoV‐2; hamster; indole‐3‐carbinol; preclinical study.