A level – Anti-Wolbachia candidates for the oral treatment of human filariasis.

Click the structures to view the 3D models

Lymphatic filariasis and onchocerciasis (river blindness) are neglected tropical diseases transmitted via filarial nematodes which host the endosymbiotic bacteria, Wolbachia. Studies have demonstrated that treatment with doxycycline results in a 90% depletion in bacterial levels of Wolbachia – which are crucial for the growth and survival of the nematode hosts.

There have been many significant breakhroughs in antibiotics development, including drugs like albendazole and doxycycline which have played a key role in treating filarial diseases. As seen above doxycycline can exist in multiple tautomeric forms, meaning it can switch between keto and enol forms. The keto form (orange) is more stable because it contains a strong C=O (carbonyl) bond. The enol form (purple) has a C=C (alkene) bond and an OH (hydroxyl) group, making it less stable. This equilibrium plays a role in doxycycline’s chemical properties and reactivity.

The use of doxycycline in particular is a good therapeutic option however, it has many limitations due to the lengthy treatment regime (4-6 weeks). This could potentially be difficult for infected individuals to adhere to due to the limited resources available in endemic regions. Due to the limitations of anti-filarial antibiotics, researchers are exploring new treatments, including the development of AWZ1066S.

For more details on the development of AWZ1066S, visit this page.

W. D. Hong, F. Benayoud, G. L. Nixon, L. Ford, K. L. Johnston, R. H. Clare, A. Cassidy, D. A. N. Cook, A. Siu, M. Shiotani, P. J. H. Webborn, S. Kavanagh, G. Aljayyoussi, E. Murphy, A. Steven, J. Archer, D. Struever, S. J. Frohberger, A. Ehrens, M. P. Hübner, A. Hoerauf, A. P. Roberts, A. T. M. Hubbard, E. W. Tate, R. A. Serwa, S. C. Leung, L. Qie, N. G. Berry, F. Gusovsky, J. Hemingway, J. D. Turner, M. J. Taylor, S. A. Ward and P. M. O’Neill, Proceedings of the National Academy of Sciences, 2019, 116, 1414-1419.