5-HT/CGRP pathway and Sumatriptan role in Covid-19

ABSTRACT

Coronavirus disease 2019 (Covid-19) is a pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). In Covid-19, there is uncontrolled activation of immune cells with a massive release of pro-inflammatory cytokines and the development of cytokine storm. These inflammatory changes induce impairment of different organ functions, including the central nervous system (CNS), leading to acute brain injury and substantial changes in the neurotransmitters, including serotonin (5-HT) and calcitonin gene-related peptide (CGRP), which have immunomodulatory properties through modulation of central and peripheral immune responses. In Covid-19, 5-HT neurotransmitters and CGRP could contribute to abnormal and atypical vascular reactivity. Sumatriptan is a pre-synaptic 5-HT (5-HT1D and 5-HT1B) agonist and inhibits the release of CGRP. Both 5-HT and CGRP seem to be augmented in Covid-19 due to underlying activation of inflammatory signaling pathways and hyperinflammation. In virtue of its anti-inflammatory and antioxidant properties with inhibition release of 5-HT and CGRP, Sumatriptan may reduce Covid-19 hyperinflammation. Therefore, Sumatriptan might be a novel potential therapeutic strategy in managing Covid-19. In conclusion, Sumatriptan could be an effective therapeutic strategy in managing Covid-19 through modulation of 5-HT neurotransmitters and inhibiting CGRP.

KEYWORDS:

• Covid-19
• SARS-CoV-2
• calcitonin gene-related peptide
• serotonin 5-HT
• Sumatriptan

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by all the authors. The first draft of the manuscript was written by Ali I. Al-Gareeb and Hayder M. Al-Kuraishy. The final editing and revisions were made by Athanasios Alexiou, Nobendu Mukerjee, Sadiq Mohammed J. Al-Hamash, Thabat J. Al-Maiahy and Gaber El-Saber Batiha. All authors read and approved the final manuscript.

Additional information

Funding

No funding details have been found for your manuscript submission, so a Funding section has been added stating that no funding was received. Please correct if this is inaccurate.