The inhibitory properties of acidic functionalised calix[4]arenes on human papillomavirus pentamer formation

ABSTRACT

Human Papillomavirus (HPV) is the leading cause of cervical cancer, with only some HPV types prevented with vaccines and no treatments for the viral infection itself. One way to target viral infection is by inhibiting the assembly of the L1 monomer into a pentamer, which forms the viral capsid. Four calix[4]arene compounds functionalised with D- and L-aspartic and glutamic acid and an iminodiacetic functionalised calix[4]arene were synthesised and tested for L1 pentamer formation inhibition. The amino acid functionalised calix[4]arene derivatives showed millimolar inhibition (IC₅₀ = 0.72 to 2.67 mM) of pentamer formation, with little difference between the stereoisomers. The iminodiacetic acid calix[4]arene derivative showed no inhibitory properties, despite sharing structural similarities with the four other calix[4]arenes. Confirmation of binding the negatively charged compounds to the positive residues of the L1 protein was achieved by trypsin digestion. This study is helpful in the development of cost-effective inhibitors to prevent HPV assembly.

Graphical abstract

KEYWORDS:

• Calixarene
• human papillomavirus
• assembly inhibitor
• L1 pentamer
• amino acid

Acknowledgments

We thank Dr Frankie Busetti of Edith Cowan University for performing the HRMS analyses on the chemical products. Ding-Yi Fu and Yuqing Wu thank the support from the National Natural Science Foundation of China (NSFC, Nos. 21875085 and 91027027).

Disclosure statement

The authors declare no potential conflict of interest.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [NSFC, Nos. 21875085 and 91027027].