Anthelmintic drug discovery: target identification, screening methods and the role of open science

Essential role of proline synthesis and the one-carbon metabolism pathways for systemic virulence of Streptococcus pneumoniae
Ramos-Sevillano, Elisa, Ercoli, Giuseppe, Betts, Modupeh, Guerra-Assunção, José Afonso, Iverson, Amy, Frank, Matthew, Partridge, Frederick, Lo, Stephanie W., Fernandes, Vitor E., Nasher, Fauzy, Wall, Emma, Wren, Brendan, Gordon, Stephen B., Ferreira, Daniela M., Heyderman, Rob, Rosch, Jason and Brown, Jeremy S. 2024. Essential role of proline synthesis and the one-carbon metabolism pathways for systemic virulence of Streptococcus pneumoniae. mBio. 15 (11), pp. e01758-24. https://doi.org/10.1128/mbio.01758-24

A drug repurposing screen for whipworms informed by comparative genomics.
Coghlan A., Partridge, F.A., Duque-Correa M.A., Rinaldi, G., Clare, S., Seymour, L., Brandt, C., Mkandawire, T.T., McCarthy, C., Holroyd, N., Nick, M., Brown, A.E. and Berriman, M. 2023. A drug repurposing screen for whipworms informed by comparative genomics. PLoS Neglected Tropical Diseases. 17 (9) e0011205. https://doi.org/10.1371/journal.pntd.0011205

Preprint: Essential role of proline synthesis and the one-carbon metabolism pathways for systemic virulence of Streptococcus pneumoniae
Ramos-Sevillano, E., Ercoli, G., Guerra-Assunção, J.A., Betts, M., Partridge, F., Fernandes, V.E., Wall, E., Gordon, S.B., Ferreira, D.M., Heyderman, R. and Brown, J.S. 2023. Preprint: Essential role of proline synthesis and the one-carbon metabolism pathways for systemic virulence of Streptococcus pneumoniae. biorxiv.org. https://doi.org/10.1101/2023.08.03.550501

Preprint: A drug repurposing screen for whipworms informed by comparative genomics
Avril Coghlan, Frederick A. Partridge, María Adelaida Duque-Correa, Gabriel Rinaldi, Simon Clare, Lisa Seymour, Cordelia Brandt, Tapoka T. Mkandawire, Catherine McCarthy, Nancy Holroyd, Marina Nick, Anwen E. Brown, Sirapat Tonitiwong, David B. Sattelle and Matthew Berriman 2023. Preprint: A drug repurposing screen for whipworms informed by comparative genomics. biorxiv.org. https://doi.org/10.1101/2023.03.02.530747

Screening the Medicines for Malaria Venture (MMV) Pandemic Response Box chemical library on Caenorhabditis elegans identifies re-profiled candidate anthelmintic drug leads
Nick, M., Partridge, F., Forman, R., Bataille, C.J.R., Else, K.J., Russell, A.J. and Sattelle, D.B. 2022. Screening the Medicines for Malaria Venture (MMV) Pandemic Response Box chemical library on Caenorhabditis elegans identifies re-profiled candidate anthelmintic drug leads. Frontiers in Tropical Diseases. 3 1017900. https://doi.org/10.3389/fitd.2022.1017900

Preprint: Screening the Medicines for Malaria Pandemic Response Box chemical library on Caenorhabditis elegans identifies re-profiled candidate anthelmintic drug leads
Nick, M., Partridge, F.A., Forman, R., Bataille, C.J.R., Else, K.J., Russell, A.J. and Sattelle, D.B. 2022. Preprint: Screening the Medicines for Malaria Pandemic Response Box chemical library on Caenorhabditis elegans identifies re-profiled candidate anthelmintic drug leads. biorxiv.org. https://doi.org/10.1101/2022.08.10.503491

Automated phenotyping of mosquito larvae enables high-throughput screening for novel larvicides and offers potential for smartphone-based detection of larval insecticide resistance
Buckingham, S.D., Partridge, F.A., Poulton, B.C., S. Miller, B.S., McKendry, R.A., Lycett, G.J. and Sattelle, D.B. 2021. Automated phenotyping of mosquito larvae enables high-throughput screening for novel larvicides and offers potential for smartphone-based detection of larval insecticide resistance. PLoS Neglected Tropical Diseases. 15 (6) e0008639. https://doi.org/10.1371/journal.pntd.0008639

Structural Requirements for Dihydrobenzoxazepinone Anthelmintics: Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni
Partridge, F.A., Bataille, C.J.R., Forman, R., Marriott, A.E., Forde-Thomas, J., Häberli, C., Dinsdale, R.L., O’Sullivan, J.D.B., Willis, N.J., Wynne, G.M., Whiteland, H., Archer, J., Steven, A., Keiser, J., Turner, J.D., Hoffmann, K.F., Taylor, M.J., Else, K.J., Russell, A.J. and Sattelle, D.B. 2021. Structural Requirements for Dihydrobenzoxazepinone Anthelmintics: Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni. ACS Infectious Diseases. 7 (5), pp. 1260-1274. https://doi.org/10.1021/acsinfecdis.1c00025

Preprint: Actions of camptothecin derivatives on larvae and adults of the arboviral vector Aedes aegypti
Partridge, F.A., Poulton, B.C., Lake, M.A.I., Lees, R.A., Mann, H-J., Lycett, G.J. and Sattelle, D.B. 2021. Preprint: Actions of camptothecin derivatives on larvae and adults of the arboviral vector Aedes aegypti. biorxiv.org. https://doi.org/10.1101/2021.09.06.458863

Preprint: Structural requirements for dihydrobenzoxazepinone anthelmintics: actions against medically important and model parasites - Trichuris muris, Brugia malayi, Heligmosomoides polygyrus and Schistosoma mansoni
Partridge, F.A., Bataille, C.J.R., Forman, R., Marriott, A.E., Forde-Thomas, J., Cécile Häberli, C., Dinsdale, R.L., O’Sullivan, J.D.B., Willis, N.J., Wynne, G.M., Whiteland, H., Archer, J., Steven, A., Keiser, J., Turner, J.D., Hoffmann, K.F., Taylor, M.J., Else, K.J., Russell, A.J. and Sattelle, D.B. 2021. Preprint: Structural requirements for dihydrobenzoxazepinone anthelmintics: actions against medically important and model parasites - Trichuris muris, Brugia malayi, Heligmosomoides polygyrus and Schistosoma mansoni. biorxiv.org. https://doi.org/10.1101/2020.11.17.384933

Preprint: Automated phenotyping of mosquito larvae enables high-throughput screening for novel larvicides and offers potential for smartphone-based detection of larval insecticide resistance
Buckingham, S.D., Partridge, F.A., Poulton, B.C., Miller, B., McKendry, R.A., Lycett, G.J. and Sattelle, D.B. 2021. Preprint: Automated phenotyping of mosquito larvae enables high-throughput screening for novel larvicides and offers potential for smartphone-based detection of larval insecticide resistance. biorxiv.org. https://doi.org/10.1101/2020.07.20.211946

Actions of Camptothecin Derivatives on Larvae and Adults of the Arboviral Vector Aedes aegypti
Partridge, F.A., Poulton, B., Lake, M.A.I., Lees, R.A., Mann, H-J., Lycett, G. and Sattelle, D.B. 2021. Actions of Camptothecin Derivatives on Larvae and Adults of the Arboviral Vector Aedes aegypti. Molecules. 26 (20) 6226. https://doi.org/10.3390/molecules26206226

C. elegans expressing D76N β2-microglobulin: a model for in vivo screening of drug candidates targeting amyloidosis
Faravelli, G., Raimondi, S., Marchese, L., Partridge, F.A., Soria, C., Mangione, P.P., Canetti, D., Perni, M., Aprile, F.A., Zorzoli, I., Di Schiavi, E., Lomas, D.A., Bellotti, V., Sattelle, D.B. and Giorgetti, S. 2019. C. elegans expressing D76N β2-microglobulin: a model for in vivo screening of drug candidates targeting amyloidosis. Scientific Reports. 9 19960. https://doi.org/10.1038/s41598-019-56498-5

Improved reference genome of Aedes aegypti informs arbovirus vector control.
Matthews, B.J., Dudchenko, O., Kingan, S.B., Koren, S., Antoshechkin, I., Crawford, J.E., Glassford, W.J., Herre, M., Redmond, S.N., Rose, N.H., Weedall, G.D., Wu, Y., Batra, S.S., Vosshall, L.B. and Partridge, F. 2018. Improved reference genome of Aedes aegypti informs arbovirus vector control. Nature. 563, pp. 501-507. https://doi.org/10.1038/s41586-018-0692-z

The fungal alkaloid Okaramine-B activates an L-glutamate-gated chloride channel from Ixodes scapularis, a tick vector of Lyme disease
Furutani, S., Ihara, M., Lees, K., Buckingham, S.D., Partridge, F.A., David, J.A., Patel, R., Warchal, S., Mellor, I.R., Matsuda, K. and Sattelle, D.B. 2018. The fungal alkaloid Okaramine-B activates an L-glutamate-gated chloride channel from Ixodes scapularis, a tick vector of Lyme disease. International Journal for Parasitology: Drugs and Drug Resistance. 8 (2), pp. 350-360. https://doi.org/10.1016/j.ijpddr.2018.06.001

2,4-Diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm
Partridge, F.A., Forman, R., Willis, N.J., Bataille, C.J.R., Murphy, E.A., Brown, A.E., Heyer-Chauhan, N., Bruno Marinič, B., Sowood, D.J.C., Wynne, G.M., Else, K.J., Russell, A.J. and Sattelle, D.B. 2018. 2,4-Diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm. PLoS Neglected Tropical Diseases. 12 (7) e0006487. https://doi.org/10.1371/journal.pntd.0006487

Preprint: 2,4-Diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm
Partridge, F.A., Forman, R., Willis, N.J., Bataille, C.J.R., Murphy, E.A., Brown, A.E., Heyer-Chauhan, N., Bruno Marinič, B., Sowood, D.J.C., Wynne, G.M., Else, K.J., Russell, A.J. and Sattelle, D.B. 2018. Preprint: 2,4-Diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm. biorxiv.org. https://doi.org/10.1101/254037

An automated high-throughput system for phenotypic screening of chemical libraries on C. elegans and parasitic nematodes
Partridge, F.A., Brown, A.E., Buckingham, S.D., Willis, N.J., Wynne, G.M., Forman, R., Else, K.J., Morrison, A.A., Matthews, J.B., Russell, A.J., Lomas, D.A. and Sattelle, D.B. 2018. An automated high-throughput system for phenotypic screening of chemical libraries on C. elegans and parasitic nematodes. International Journal for Parasitology: Drugs and Drug Resistance. 8 (1), pp. 8-21. https://doi.org/10.1016/j.ijpddr.2017.11.004

Dihydrobenz[e][1,4]oxazepin-2(3H)-ones, a new anthelmintic chemotype immobilising whipworm and reducing infectivity in vivo.
Partridge, F.A., Murphy, E.A., Willis, N.J., Bataille, C.J., Forman, R., Heyer-Chauhan, N., Marinič, B., Sowood, D.J., Wynne, G.M., Else, K.J., Russell, A.J. and Sattelle, D.B. 2017. Dihydrobenz[e][1,4]oxazepin-2(3H)-ones, a new anthelmintic chemotype immobilising whipworm and reducing infectivity in vivo. PLoS Neglected Tropical Diseases. 11 (2) e0005359. https://doi.org/10.1371/journal.pntd.0005359

Preprint: Improved Aedes aegypti mosquito reference genome assembly enables biological discovery and vector control
Matthews, B.J., Dudchenko, O., Kingan, S., Koren, S., Antoshechkin, I., Crawford, J.E., Glassford, W.J., Herre, M., Redmond, S.N., Rose, N.H., Weedall, G.D., Wu, Y., Batra, S.S., Vosshall, L.B. and Partridge, F. 2017. Preprint: Improved Aedes aegypti mosquito reference genome assembly enables biological discovery and vector control. https://doi.org/10.1101/240747

Preprint: An automated high-throughput system for phenotypic screening of chemical libraries on C. elegans and parasitic nematodes
Partridge, F.A., Brown, A.E., Buckingham, S.D., Willis, N.J., Wynne, G.M., Forman, R., Else, K.J., Morrison, A.A., Matthews, J.B., Russell, A.J., Lomas, D.A. and Sattelle, D.B. 2017. Preprint: An automated high-throughput system for phenotypic screening of chemical libraries on C. elegans and parasitic nematodes. biorxiv.org. https://doi.org/10.1101/187427

Automated, high-throughput, motility analysis in Caenorhabditis elegans and parasitic nematodes: Applications in the search for new anthelmintics
Buckingham, S.D., Partridge, F.A. and Sattelle, D.B. 2014. Automated, high-throughput, motility analysis in Caenorhabditis elegans and parasitic nematodes: Applications in the search for new anthelmintics. International Journal for Parasitology: Drugs and Drug Resistance. 4 (3), pp. 226-232. https://doi.org/10.1016/j.ijpddr.2014.10.004

An antagonist of the retinoid X receptor reduces the viability of Trichuris muris in vitro.
Hurst, R.J., Hopwood, T., Gallagher, A.L., Partridge, F.A., Burgis, T., Sattelle, D.B. and Else, K.J. 2014. An antagonist of the retinoid X receptor reduces the viability of Trichuris muris in vitro. BMC Infectious Diseases. https://doi.org/10.1186/1471-2334-14-520

Serotonergic chemosensory neurons modify the C. elegans immune response by regulating G-protein signaling in epithelial cells.
Anderson, A., Laurenson-Schafer, H., Partridge, F.A., Hodgkin, J. and McMullan, R. 2013. Serotonergic chemosensory neurons modify the C. elegans immune response by regulating G-protein signaling in epithelial cells. PLOS Pathogens. 9 (12) e1003787. https://doi.org/10.1371/journal.ppat.1003787

Signal transduction pathways that function in both development and innate immunity.
Partridge, F.A., Gravato-Nobre, M.J. and Hodgkin, J. 2010. Signal transduction pathways that function in both development and innate immunity. Developmental Dynamics. 239 (5), pp. 1330-1336. https://doi.org/10.1002/dvdy.22232

The C. elegans glycosyltransferase BUS-8 has two distinct and essential roles in epidermal morphogenesis.
Partridge, F.A., Tearle, A.W., Gravato-Nobre, M.J., Schafer, W.R. and Hodgkin, J. 2008. The C. elegans glycosyltransferase BUS-8 has two distinct and essential roles in epidermal morphogenesis. Developmental Biology. 317 (2), pp. 549-559. https://doi.org/10.1016/j.ydbio.2008.02.060

Caenorhabditis elegans meets microsporidia: the nematode killers from Paris.
Hodgkin, J. and Partridge, F.A. 2008. Caenorhabditis elegans meets microsporidia: the nematode killers from Paris. PLOS Biology. 6 (12) e1000005. https://doi.org/10.1371/journal.pbio.1000005