Dihydroergotamine may improve body clock disorders by interacting with the CRY1 protein

Dihydroergotamine (DHE) was identified as the top candidate for treating circadian rhythm disorders from a screening of 1429 FDA-approved small molecules.

• The study utilized a multi-scale virtual screening approach to assess small molecules against five circadian rhythm-related proteins.
• DHE demonstrated favorable binding profiles and minimal predicted adverse effects on gut microbiota.
• Molecular dynamics simulations indicated stable interactions of the DHE-6KX4 complex over a 100 ns simulation time.
• DHE alleviated sleep deprivation-induced physiological and behavioral abnormalities, including weight loss and memory deficits.
• Mechanistically, DHE promoted the accumulation of the PER1-CRY1 complex in the nucleus, suppressing CLOCK expression and restoring circadian rhythm function.
• The interaction between DHE and CRY1 is a computational prediction that requires further experimental validation.

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