biostudies-literatureHubner MPJürgen Manchot foundationBill & Melinda Gates FoundationCalibr at Scripps Research18-27https://www.ebi.ac.uk/biostudies/studies/S-EPMC6931063biostudies-literatureUnknown12The quinazolines CBR417 and CBR490 were previously shown to be potent anti-wolbachials that deplete Wolbachia endosymbionts of filarial nematodes and present promising pre-clinical candidates for human filarial diseases such as onchocerciasis. In the present study we tested both candidates in two models of chronic filarial infection, namely the Litomosoides sigmodontis and Brugia pahangi jird model and assessed their long-term effect on Wolbachia depletion, microfilariae counts and filarial embryogenesis 16-18 weeks after treatment initiation (wpt). Once per day (QD) oral treatment with CBR417 (50 mg/kg) for 4 days or twice per day (BID) with CBR490 (25 mg/kg) for 7 days during patent L. sigmodontis infection reduced the Wolbachia load by >99% and completely cleared peripheral microfilaremInternational journal for parasitology. Drugs and drug resistanceShort-course quinazoline drug treatments are effective in the Litomosoides sigmodontis and Brugia pahangi jird models.PMC6931063OPP1107194OPP1134310OPP1017584OPP1119043Bulman CAFrohberger SJBakowski MATurner JDFendler MPetrassi HMMcNamara CWEhrens AHubner MPChi VKoschel MSullivan WSteven AVogel ILim KCGunderson EChappell LVoronin DTaylor MJBeerntsen BHoerauf ATricoche NSakanari JAWoods AKLustigman SfalseShort-course quinazoline drug treatments are effective in the Litomosoides sigmodontis and Brugia pahangi jird models.The quinazolines CBR417 and CBR490 were previously shown to be potent anti-wolbachials that deplete Wolbachia endosymbionts of filarial nematodes and present promising pre-clinical candidates for human filarial diseases such as onchocerciasis. In the present study we tested both candidates in two models of chronic filarial infection, namely the Litomosoides sigmodontis and Brugia pahangi jird model and assessed their long-term effect on Wolbachia depletion, microfilariae counts and filarial embryogenesis 16-18 weeks after treatment initiation (wpt). Once per day (QD) oral treatment with CBR417 (50 mg/kg) for 4 days or twice per day (BID) with CBR490 (25 mg/kg) for 7 days during patent L. sigmodontis infection reduced the Wolbachia load by >99% and completely cleared peripheral microfilarem2020-01-01T00:00:00Z2020 Apr2026-04-14T13:12:08.448Z2020-05-22T01:16:58ZS-EPMC69310633186975910.1016/j.ijpddr.2019.12.001