Treating autoimmune disorders with venom-derived peptides

ABSTRACT

Introduction: The effective treatment of autoimmune diseases remains a challenge. Voltage-gated potassium Kv1.3 channels, which are expressed in lymphocytes, are a new therapeutic target for treating autoimmune disease. Consequently, Kv1.3 channel-inhibiting venom-derived peptides are a prospective resource for new drug discovery and clinical application.

Area covered: Preclinical and clinical studies have produced a wealth of information on Kv1.3 channel-inhibiting venom-derived peptides, especially from venomous scorpions and sea anemones. This review highlights the advances in screening and design of these peptides with diverse structures and potencies. It focuses on representative strategies for improving peptide selectivity and discusses the preclinical research on those venom-derived peptides as well as their clinical developmental status.

Expert opinion: Encouraging results indicate that peptides isolated from the venom of venomous animals are a large resource for discovering immunomodulators that act on Kv1.3 channels. Since the structural diversity of venom-derived peptides determines the variety of their pharmacological activities, the design and optimization of venom-peptides for improved Kv1.3 channel-specificity has been advanced through some representative strategies, such as peptide chemical modification, amino acid residue truncation and binding interface modulation. These advances should further accelerate research, development and the future clinical application of venom-derived peptides selectively targeting Kv1.3 channels.

KEYWORDS:

• Autoimmune disorders
• lymphocytes
• potassium channel Kv1.3
• venom-derived peptides
• selectivity improvement

Article highlights

• Kv1.3 channels in lymphocytes are new therapeutic targets for treating autoimmune diseases.

• Potassium channel-specific peptides from venomous animals are a huge resource in terms of Kv1.3 channel inhibitor discovery.

• Given the multi-potassium channel blocking effects of toxin peptides, the question of how to further improve the selectivity of toxin peptides and reduce their potential side has been of interest to researchers.

• Venom-derived peptides have demonstrated promise through preclinical and clinical studies for treating autoimmune disorders.

• The discovery of highly potent and selective Kv1.3 channel-acting venom-derived peptides remains a challenge.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was supported by grants from the National Natural Sciences Foundation of China [No. 81630091], the State Key Project of Research and Development Plan (No. 2016YFE0122800), the Hubei Natural Sciences Foundation [No. 2016CFA018], and the Open Research Fund Program of the State Key Laboratory of Virology of China [No. 2016KF002].