Table 1.
Overview of current and prospective anti-filarial compounds
| Name | Mode of action | Status | Effect | Class | Clinical trials [ID] | Source |
|---|---|---|---|---|---|---|
| Doxycycline | Binds 30S ribosomal subunit, inhibition of protein synthesis | Used in individual therapy for onchocerciasis and lymphatic filariasis | Wolbachia depletion/macrofilaricide | Tetrazycline |
ISRCTN65756724 [LF] ISRCTN14042737 [LF] ISRCTN06010453 [Oncho] ISRCTN68861628 [Oncho] ISRCTN71141922 [Oncho] |
Klarman-Schulz et al. 2017 Taylor et al. 2010 Debrah et al. 2007 Debrah et al. 2015 |
| Rifampicin | Binds DNA-dependent RNA-polymerase, inhibition of translation | Phase II clinical studies with the standard low dose have been performed. High dose clinical studies are scheduled. | Wolbachia depletion/potential macrofilaricide | Rifamycin |
ISRCTN68861628 [Oncho] ISRCTN15216778 [LF] |
Aljayyoussi et al. 2017 |
| ABBV-4083 | Binds 50S ribosomal subunit, inhibition of protein synthesis | Phase I clinical studies completed. Phase II clinical studies under preparation. | Wolbachia depletion/potential macrofilaricide | Macrolide | Taylor et al. 2019 | |
| AWZ-1066S | Inhibits protein synthesis | Under preparation for phase 1 clinical studies | Wolbachia depletion/potential macrofilaricide | Azaquinazoline | Hong et al. 2019 | |
| AN11251 | Binds 50S ribosomal subunit, inhibition of protein synthesis | Backup clinical candidate | Wolbachia depletion/potential macrofilaricide | Pleuromutilin | Jacobs et al. 2019 | |
| Corallopyronin A | Inhibits DNA-dependent RNA-polymerase | under preparation for phase 1 clinical studies | Wolbachia depletion/potential macrofilaricide | α-Pyrone |
Schiefer et al. 2012 Schiefer et al. 2020 |
|
| Ivermectin (IVM) | Interferes with ligand-gated chloride channels | Used against onchocerciasis and lymphatic filariasis as mass drug administrations. | Microfilaricide | Avermectin | ISRCTN50035143 [Oncho] |
Richard-Lenoble et al. 2003 Laing et al. 2017 |
| Moxidectin | Exact mode of action is unknown | Potential alternative to ivermectin for mass drug administrations | Microfilaricide | Milbemycine | ISRCTN50035143 [Oncho] |
Milton et al. 2020 Opoku et al. 2018 |
| Diethylcarbamazine (DEC) | Alters metabolism of arachidonic acid | Used against lymphatic filariasis as part of mass drug administrations. Contraindicated in onchocerciasis patients | Microfilaricide | Piperazines | ISRCTN76875372 [Oncho] | Maizels and Denham 1992 |
| Albendazole | Inhibits tubulin polymerization | Used against lymphatic filariasis as part of mass drug administrations; used in conjunction with diethylcarbamazine and/or ivermectin | May improve microfilaricidal efficacy of IVM/DEC | Benzimidazole |
ISRCTN50035143 [Oncho] ISRCTN06010453 [Oncho] ISRCTN25831558 [Loiasis] ISRCTN56578422 [LF] |
Macfarlane et al. 2019 |
| Flubendazole | Inhibits tubulin polymerization | Currently not recommended for clinical use against human filarial diseases due to possible adverse events and limited bioavailability after oral treatment. | Potential macrofilaricide | Benzimidazole |
Geary et al. 2019 Lachau-Durand et al. 2019 |
|
| Oxfendazole | Inhibits tubulin polymerization | Phase I clinical studies completed. | Potential macrofilaricide | Benzimidazole |
Hübner et al. 2020 Gonzalez et al. 2019 |
|
| Emodepside | Interferes with potassium channel SLO-1 | Phase I clinical studies completed. Phase II clinical studies under preparation. | Potential macrofilaricide | Cyclooctadepsipeptide | Kulke et al. 2017 |