Inhibition of influenza H5N1 invasion by modified heparin derivatives

Skidmore, Mark A.; Kajaste-Rudnitski, Anna; Wells, Nicola M.; Guimond, Scott E.; Rudd, Timothy R.; Yates, Edwin A.; Vicenzi, Elisa

Abstract

Influenza remains a serious health threat, with resistance to frontline drugs becoming more common, and new treatments urgently sought. One strategy for the inhibition of the attachment of influenza to host cells is to employ chemically modified heparins, capable of effectively competing with the multivalent interactions involved. In an assay of H5N1 influenza viral invasion comprising a H5 pseudotyped HIV system, selective removal of the sulfate groups from heparin (IC50 ~22 × 10−9 g mL−1) allowed the retention of inhibitory activity in the products (IC50 ~4 × 10−9 g mL−1) while significantly reducing their anticoagulant activities. Chemically modified anionic polysaccharides offer a potential source of effective inhibitors of viral attachment, which are suitable for further optimisation.

Citation

Skidmore, M. A., Kajaste-Rudnitski, A., Wells, N. M., Guimond, S. E., Rudd, T. R., Yates, E. A., & Vicenzi, E. Inhibition of influenza H5N1 invasion by modified heparin derivatives. MedChemComm, 6(4), 640-646. https://doi.org/10.1039/c4md00516c

• Journal Article Type: Article
• Deposit Date: May 31, 2023
• Journal: MedChemComm
• Print ISSN: 2040-2503
• Electronic ISSN: 2040-2511
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 4
• Pages: 640-646
• DOI: https://doi.org/10.1039/c4md00516c
• Keywords: Pharmaceutical Science; Biochemistry; Drug Discovery; Molecular Medicine; Pharmacology; Organic Chemistry
• Additional Information: : This document is Similarity Check deposited; : Supplementary Information; : The Royal Society of Chemistry has an exclusive publication licence for this journal; OPEN ACCESS: The accepted version of this article will be made freely available after a 12 month embargo period; : Single-blind; : Received 12 November 2014; Accepted 19 December 2014; Accepted Manuscript published 23 December 2014; Advance Article published 7 January 2015; Version of Record published 10 April 2015