key: cord-0697968-fyis055p authors: Kow, Chia Siang; Ramachandram, Dinesh Sangarran; Hasan, Syed Shahzad title: Use of sulforaphane in COVID-19: clinical trials are needed date: 2022-03-07 journal: Mol Immunol DOI: 10.1016/j.molimm.2022.03.001 sha: 5205882979cacea01242f392a453e416d5f47cae doc_id: 697968 cord_uid: fyis055p We read with interest the narrative review authored by Kiser et al. (2021), which discussed extensively the antioxidant effect and anti-inflammatory effect of sulforaphane, a dietary supplement found in high amounts in cruciferous vegetables that are naturally occurring, orally accessible, and well-tolerated. Notably, in their review, the authors also discussed the potential use of sulforaphane in patients with coronavirus disease 2019 (COVID-19). We believe such discussion is useful since the researchers are still searching for potential drugs to be repurposed for the treatment of COVID-19 to expand our armamentarium against this deadly disease. We read with interest the narrative review authored by Kiser et al. (2021) , which discussed extensively the antioxidant effect and anti-inflammatory effect of sulforaphane, a dietary supplement found in high amounts in cruciferous vegetables that are naturally occurring, orally accessible, and well-tolerated. Notably, in their review, the authors also discussed the potential use of sulforaphane in patients with coronavirus disease 2019 . We believe such discussion is useful since the researchers are still searching for potential drugs to be repurposed for the treatment of COVID-19 to expand our armamentarium against this deadly disease. We read with interest the narrative review authored by Kiser et al. (2021) , which discussed extensively the antioxidant effect and anti-inflammatory effect of sulforaphane, a dietary supplement found in high amounts in cruciferous vegetables that are naturally occurring, orally accessible, and well-tolerated. Notably, in their review, the authors also discussed the potential use of sulforaphane in patients with coronavirus disease 2019 . We believe such discussion is useful since the researchers are still searching for potential drugs to be repurposed for the treatment of COVID-19 to expand our armamentarium against this deadly disease. In their review, the authors suggested that sulforaphane can be beneficial to patients with COVID-19 via its two notable mechanisms of action, namely activation of nuclear factor-erythroid factor 2-J o u r n a l P r e -p r o o f related factor 2 (NRF2) and inhibition of nuclear factor kappa B (NF-κB) (Kiser et al., 2021) . Indeed, given that a previous study (Olagnier et al., 2020) has reported that the expression pathway of the NRF2 antioxidant gene was found to be suppressed in the lung biopsies obtained from patients with COVID-19, sulforaphane as a potent NRF2 inducer could improve the prognosis of this population of patients. In addition, NF-κB activation and the consequent release of associated cytokines can contribute to the development of cytokine storm in patients with COVID-19, and thus the inhibitory effects of sulforaphane on the NF-κB pathway appear salutary to patients with COVID-19 (Su et al., 2021) . Nevertheless, while the authors acknowledge the inhibitory effects of sulforaphane on NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation, it has not been discussed as one of the potential mechanisms where sulforaphane can be useful for patients with COVID-19. Sulforaphane mediates the inhibitory effect on NLRP3 inflammasome activation independent of the NRF2 pathway through decreased miR-155 expression and increased miR-223 expression (Tufekci et al., 2021) . We felt that this could be the main mechanism where sulforaphane is useful for patients with COVID-19 since the N protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative pathogen of COVID-19, has been found to directly interact and promote NLRP3 inflammasome activation to induce inflammatory responses in patients with COVID-19 (Pan et al., 2021) . Hence, targeting the NLRP3 inflammasome with sulforaphane appears to be a promising intervention against COVID-19. In fact, in the cultured IB3-1 bronchial cells, sulforaphane has been found to inhibit the gene expression of interleukin (IL)-6 and IL-8, which are the downstream cytokines of NLRP3 inflammasome involved in the cytokine storm of COVID-19 (Gasparello et al., 2021) . Most importantly, sulforaphane also demonstrates antiviral activity against SARS-CoV-2, inhibiting in vitro replication of four strains of SARS-CoV-2. Besides, administration of sulforaphane to K18-hACE2 mice prior to intranasal SARS-CoV-2 infection significantly reduced the viral load in the respiratory tract. (Ordonez et al., 2021) . All in all, the anti-inflammatory and antiviral effects of sulforaphane should be utilized in combat against COVID-19. We look forward to the performance of clinical trials to validate the clinical efficacy of sulforaphane in patients with COVID-19. Sulforaphane inhibits the expression of interleukin-6 and interleukin-8 induced in bronchial epithelial IB3-1 cells by exposure to the SARS-CoV-2 Spike protein Inhibitory effects of sulforaphane on NLRP3 inflammasome activation SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate Sulforaphane exhibits in vitro and in vivo antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses. bioRxiv : the preprint server for biology SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation Activation of NF-κB and induction of proinflammatory cytokine expressions mediated by ORF7a protein of SARS-CoV-2 Sulforaphane inhibits NLRP3 inflammasome activation in microglia through Nrf2-mediated miRNA alteration All authors declare no conflicts of interest.