“When you inhibit caspase 11, you get rid of many cytokines, which damage the lung tissue and the blood-brain barrier and brain tissue,” Amer said. “Combining that together with stopping viral replication is going to be very effective at reducing deaths and severe illness from SARS-CoV-2 infection, and reducing the post-infection symptoms experienced by people with long COVID.”
They also mention caspase 4:
The 2022 published research showed in mice infected with SARS-CoV-2 that blocking this molecule, an enzyme called caspase 11, resulted in lower inflammation and tissue injury and fewer blood clots in the animals’ lungs. The researchers also found that the human version of the enzyme, called caspase 4, was highly expressed in COVID-19 patients hospitalized in the ICU – confirming the molecule’s link to severe disease.
“NSAIDs comprised half of the hits, and eight of the top ten most potent inhibitors” but “naproxen and ibuprofen are weak inhibitors”. Surprisingly the α-adrenergic blockers terazosin and prazosin were also good hits. Also resveratrol.
Caspase-11, an important enzyme in the inflammatory response, can be inhibited by several mechanisms and compounds:
Small Molecules: Compounds like FeTPPS can inhibit caspase-11 by binding to high mobility group box 1 (HMGB1), which is involved in the activation of caspase-11 during sepsis².
Berberine Alkaloids: These inhibit the caspase-11 pathway by preventing the cytosolic translocation of lipopolysaccharide (LPS), which is necessary for caspase-11 activation⁵.
Indirect Inhibitors: Compounds such as VX-765, Z-VAD-FMK, and Ac-YVAD-CMK, while primarily targeting other caspases, can indirectly influence caspase-11 due to the interconnected nature of inflammatory signaling pathways⁴.
These inhibitors are significant in research and potential therapeutic applications, especially in conditions like sepsis where caspase-11 plays a critical role.