Long Covid and caspase 11 & 4

Finding a solution for long COVID, one cell type at a time 2024

“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.

See also: The cure for long COVID may come from Ohio 2024

Do we know caspase 11 inhibitors?

For caspase 4, I found: Non-steroidal Anti-inflammatory Drugs Are Caspase Inhibitors 2017

“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.

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Caspase-11, an important enzyme in the inflammatory response, can be inhibited by several mechanisms and compounds:

  1. 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.
  2. Berberine Alkaloids: These inhibit the caspase-11 pathway by preventing the cytosolic translocation of lipopolysaccharide (LPS), which is necessary for caspase-11 activation⁵.
  3. 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.

Source: Conversation with Copilot, 9/6/2024
(1) A small molecule binding HMGB1 inhibits caspase-11-mediated … - Nature. https://www.nature.com/articles/s41419-021-03652-5.pdf.
(2) Blocking Msr1 by berberine alkaloids inhibits caspase-11 … - Nature. https://www.nature.com/articles/s41392-021-00483-w.pdf.
(3) caspase-11 Inhibitors | SCBT - Santa Cruz Biotechnology. caspase-11 Inhibitors | SCBT - Santa Cruz Biotechnology.
(4) Caspase-11 Non-canonical Inflammasomes in the Lung. Frontiers | Caspase-11 Non-canonical Inflammasomes in the Lung.
(5) caspase-11 Inhibitors | SCBT - Santa Cruz Biotechnology. what inhibits caspase 11 - Search.
(6) Caspase-11 promotes allergic airway inflammation - Nature. https://www.nature.com/articles/s41467-020-14945-2.pdf.
(7) undefined. Frontiers | Caspase-11 Non-canonical Inflammasomes in the Lung.
(8) undefined. A small molecule binding HMGB1 inhibits caspase-11-mediated lethality in sepsis | Cell Death & Disease.
(9) CDD6 11 4. - Nature. https://www.nature.com/articles/4400594.pdf.
(10) A Review on Caspases: Key Regulators of Biological … - Springer. https://link.springer.com/content/pdf/10.1007/s12035-023-03433-5.pdf.
(11) A long way to go: caspase inhibitors in clinical use - Nature. https://www.nature.com/articles/s41419-021-04240-3.pdf.

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