tetano
Editor, Senior Moderator
iScience
. 2023 Aug 16;26(9):107631.
doi: 10.1016/j.isci.2023.107631. eCollection 2023 Sep 15. Combating pan-coronavirus infection by indomethacin through simultaneously inhibiting viral replication and inflammatory response
Yining Wang[SUP] 1 [/SUP], Pengfei Li[SUP] 1 [/SUP], Lei Xu[SUP] 1 2 [/SUP], Annemarie C de Vries[SUP] 1 [/SUP], Robbert J Rottier[SUP] 3 4 [/SUP], Wenshi Wang[SUP] 1 5 [/SUP], Marie-Rose B S Crombag[SUP] 6 [/SUP], Maikel P Peppelenbosch[SUP] 1 [/SUP], Denis E Kainov[SUP] 7 8 [/SUP], Qiuwei Pan[SUP] 1 [/SUP]
Affiliations
Severe infections with coronaviruses are often accompanied with hyperinflammation, requiring therapeutic strategies to simultaneously tackle the virus and inflammation. By screening a safe-in-human broad-spectrum antiviral agents library, we identified that indomethacin can inhibit pan-coronavirus infection in human cell and airway organoids models. Combining indomethacin with oral antiviral drugs authorized for treating COVID-19 results in synergistic anti-coronavirus activity. Coincidentally, screening a library of FDA-approved drugs identified indomethacin as the most potent potentiator of interferon response through increasing STAT1 phosphorylation. Combining indomethacin with interferon-alpha exerted synergistic antiviral effects against multiple coronaviruses. The anti-coronavirus activity of indomethacin is associated with activating interferon response. In a co-culture system of lung epithelial cells with macrophages, indomethacin inhibited both viral replication and inflammatory response. Collectively, indomethacin is a pan-coronavirus inhibitor that can simultaneously inhibit virus-triggered inflammatory response. The therapeutic potential of indomethacin can be further augmented by combining it with oral antiviral drugs or interferon-alpha.
Keywords: Drugs; Immune response; Virology.
. 2023 Aug 16;26(9):107631.
doi: 10.1016/j.isci.2023.107631. eCollection 2023 Sep 15. Combating pan-coronavirus infection by indomethacin through simultaneously inhibiting viral replication and inflammatory response
Yining Wang[SUP] 1 [/SUP], Pengfei Li[SUP] 1 [/SUP], Lei Xu[SUP] 1 2 [/SUP], Annemarie C de Vries[SUP] 1 [/SUP], Robbert J Rottier[SUP] 3 4 [/SUP], Wenshi Wang[SUP] 1 5 [/SUP], Marie-Rose B S Crombag[SUP] 6 [/SUP], Maikel P Peppelenbosch[SUP] 1 [/SUP], Denis E Kainov[SUP] 7 8 [/SUP], Qiuwei Pan[SUP] 1 [/SUP]
Affiliations
- PMID: 37664584
- PMCID: PMC10474465
- DOI: 10.1016/j.isci.2023.107631
Severe infections with coronaviruses are often accompanied with hyperinflammation, requiring therapeutic strategies to simultaneously tackle the virus and inflammation. By screening a safe-in-human broad-spectrum antiviral agents library, we identified that indomethacin can inhibit pan-coronavirus infection in human cell and airway organoids models. Combining indomethacin with oral antiviral drugs authorized for treating COVID-19 results in synergistic anti-coronavirus activity. Coincidentally, screening a library of FDA-approved drugs identified indomethacin as the most potent potentiator of interferon response through increasing STAT1 phosphorylation. Combining indomethacin with interferon-alpha exerted synergistic antiviral effects against multiple coronaviruses. The anti-coronavirus activity of indomethacin is associated with activating interferon response. In a co-culture system of lung epithelial cells with macrophages, indomethacin inhibited both viral replication and inflammatory response. Collectively, indomethacin is a pan-coronavirus inhibitor that can simultaneously inhibit virus-triggered inflammatory response. The therapeutic potential of indomethacin can be further augmented by combining it with oral antiviral drugs or interferon-alpha.
Keywords: Drugs; Immune response; Virology.