Target-agnostic identification of human antibodies to Plasmodium falciparum sexual forms reveals cross stage recognition of glutamate-rich repeats By Jessica Konijnenburg18/07/202419/07/2024 Categories: Publications A. Amen et al., eLife, 2024 ABSTRACT Circulating sexual stages of Plasmodium falciparum (Pf) can be transmitted from humans to mosquitoes, thereby furthering the spread of malaria in the population….
2,8-Disubstituted-1,5-naphthyridines as Dual Inhibitors of Plasmodium falciparum Phosphatidylinositol-4-kinase and Hemozoin Formation with In Vivo Efficacy By Jessica Konijnenburg18/07/202419/07/2024 Categories: Publications G. A. Dziwornu et al. Journal of Medicinal Chemistry (13), 2024 ABSTRACT Structure–activity relationship studies of 2,8-disubstituted-1,5-naphthyridines, previously reported as potent inhibitors of Plasmodium falciparum (Pf) phosphatidylinositol-4-kinase β…
Assessment of the transmission blocking activity of antimalarial compounds by membrane feeding assays using natural Plasmodium falciparum gametocyte isolates from West-Africa By Jessica Konijnenburg28/07/2023 Categories: Publications N.B. Henry et al., PLOS One, 2023 ABSTRACT Antimalarial drugs that can block the transmission of Plasmodium gametocytes to mosquito vectors would be highly beneficial for malaria elimination efforts. Identifying…
A versatile Plasmodium falciparum reporter line expressing NanoLuc enables highly sensitive multi-stage drug assays By Jessica Konijnenburg28/07/2023 Categories: Publications Y. Miyazaki et al., Communications biology (6), 2023 ABSTRACT Transgenic luciferase-expressing Plasmodium falciparum parasites have been widely used for the evaluation of anti-malarial compounds. Here, to screen for…
Metabolic activity organizes olfactory representations By Jessica Konijnenburg12/05/2023 Categories: Publications W. Qian et al., eLife 12, 2023 ABSTRACT Hearing and vision sensory systems are tuned to the natural statistics of acoustic and electromagnetic energy on earth and are…
Assessment of the drugability of initial malaria infection through miniaturized sporozoite assays and high-throughput screening By Jessica Konijnenburg03/03/2023 Categories: Publications M. Miglianico et al., Communications Biology 6(1), 2023 ABSTRACT The sporozoite stages of malaria parasites are the primary cause of infection of the vertebrate host and are targeted…
Potent transmission-blocking monoclonal antibodies from naturally exposed individuals target a conserved epitope on Plasmodium falciparum Pfs230 By Jessica Konijnenburg27/02/202327/02/2023 Categories: Publications D. Ivanoschko et al., Immunity (56), 2023 ABSTRACT Pfs230 is essential for Plasmodium falciparum transmission to mosquitoes and is the protein targeted by the most advanced malaria-transmission-blocking vaccine…
Highly potent, naturally acquired human monoclonal antibodies against Pfs48/45 block Plasmodium falciparum transmission to mosquitoes By Jessica Konijnenburg27/02/2023 Categories: Publications A. Fabra-Garcia et al., Immunity (56), 2023 ABSTRACT Malaria transmission-blocking vaccines (TBVs) aim to induce antibodies that interrupt malaria parasite development in the mosquito, thereby blocking onward transmission,…
Creation and preclinical evaluation of genetically attenuated malaria parasites arresting growth late in the liver By Jessica Konijnenburg05/01/2023 Categories: Publications B. Franke-Fayard et al., npj Vaccines 7, 2022 ABSTRACT Whole-sporozoite (WSp) malaria vaccines induce protective immune responses in animal malaria models and in humans. A recent clinical trial…
Replenishing the malaria drug discovery pipeline: Screening and hit evaluation of the MMV Hit Generation Library 1 (HGL1) against asexual blood stage Plasmodium falciparum, using a nano luciferase reporter read-out By Koen Dechering29/07/202223/08/2022 Categories: Publications K. Dechering et al., SLAS Discovery (22), 2022 ABSTRACT A central challenge of antimalarial therapy is the emergence of resistance to the components of artemisinin-based combination therapies (ACTs)…
Preclinical characterization and target validation of the antimalarial pantothenamide MMV693183 By Koen Dechering21/04/202223/08/2022 Categories: Publications L.E. de Vries et al., Nature Communications 13(1), 2022 ABSTRACT Drug resistance and a dire lack of transmission-blocking antimalarials hamper malaria elimination. Here, we present the pantothenamide MMV693183…
The Nitrobenzoxadiazole Derivative NBDHEX Behaves as Plasmodium falciparum Gametocyte Selective Inhibitor with Malaria Parasite Transmission Blocking Activity By Koen Dechering29/01/202223/08/2022 Categories: Publications G. Siciliano et al., Pharmaceuticals 15(2), 2022 ABSTRACT This work describes the activity of 6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexan-1-ol (NBDHEX) and of its newly identified carboxylic acid metabolite on the human malaria…
Barcoded Asaia bacteria enable mosquito in vivo screens and identify novel systemic insecticides and inhibitors of malaria transmission By Koen Dechering21/12/202129/07/2022 Categories: Publications A. Sturm et al., PLOS Biology 19(12) 2021 ABSTRACT This work addresses the need for new chemical matter in product development for control of pest insects and vector-borne…
Prioritization of Molecular Targets for Antimalarial Drug Discovery By Jessica Konijnenburg17/09/2021 Categories: Publications B. Forte et al., ACS Infect Dis. 2021 Sep 15 ABSTRACT There is a shift in antimalarial drug discovery from phenotypic screening toward target-based approaches, as more potential…
Discovery and Structure-Activity Relationships of Quinazolinone-2-carboxamide Derivatives as Novel Orally Efficacious Antimalarials By Jessica Konijnenburg31/08/202131/08/2021 Categories: Publications Laleu B., et al., J Med Chem. 2021 Aug 26 ABSTRACT A phenotypic high-throughput screen allowed discovery of quinazolinone-2-carboxamide derivatives as a novel antimalarial scaffold. Structure-activity relationship studies…
MalDA, Accelerating Malaria Drug Discovery By Jessica Konijnenburg10/07/202131/08/2021 Categories: Publications Yang et al., Trends Parasitol. 2021 Jul 7 ABSTRACT The Malaria Drug Accelerator (MalDA) is a consortium of 15 leading scientific laboratories. The aim of MalDA is to…
Repositioning and Characterization of 1-(Pyridin-4-yl)pyrrolidin-2-one Derivatives as Plasmodium Cytoplasmic Prolyl-tRNA Synthetase Inhibitors By Jessica Konijnenburg15/06/202131/08/2021 Categories: Publications Okaniwa et al., ACS Infect Dis. 2021 jun 11 ABSTRACT Prolyl-tRNA synthetase (PRS) is a clinically validated antimalarial target. Screening of a set of PRS ATP-site binders, initially…
Generation of a Genetically Modified Chimeric Plasmodium falciparum Parasite Expressing Plasmodium vivax Circumsporozoite Protein for Malaria Vaccine Development By Jessica Konijnenburg21/12/202031/08/2021 Categories: Publications Miyazaki et al., Front Cell Infect Micorbiol. 2020 Dec 17 ABSTRACT Chimeric rodent malaria parasites with the endogenous circumsporozoite protein (csp) gene replaced with csp from the human parasites Plasmodium falciparum (Pf)…
The Plasmodium falciparum circumsporozoite protein produced in Lactococcus lactis is pure and stable. By Jessica Konijnenburg11/01/202020/02/2020 Categories: Publications Singh, S.K. et al., J Biol Chem. 2020 Jan 10 ABSTRACT The Plasmodium falciparum circumsporozoite protein (PfCSP) is a sporozoite surface protein whose role in sporozoite motility and cell invasion…
Antimalarial pantothenamide metabolites target acetyl–coenzyme A biosynthesis in Plasmodium falciparum By Jessica Konijnenburg19/09/201919/09/2019 Categories: Publications Schalkwijk et al., Sci. Transl. Med 2019 Sept 19 ABSTRACT Malaria eradication is critically dependent on new therapeutics that target resistant Plasmodium parasites and block transmission of the…
Repurposing isoxazoline veterinary drugs for control of vector-borne human diseases By Jessica Konijnenburg03/07/201803/07/2018 Categories: Publications Miglianico M. et al., PNAS 2018 July 02 ABSTRACT Isoxazolines are oral insecticidal drugs currently licensed for ectoparasite control in companion animals. Here we propose their use in…
Antimalarial agents against both sexual and asexual parasites stages: structure-activity relationships and biological studies of the Malaria Box compound 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine (MMV019918) and analogues. By Jessica Konijnenburg10/03/201828/03/2018 Categories: Publications Vallone et al., Eur J Med Chem. 2018 Mar 10 ABSTRACT Therapies addressing multiple stages of Plasmodium falciparum life cycle are highly desirable for implementing malaria elimination strategies….
Modelling mosquito infection at natural parasite densities identifies drugs targeting EF2, PI4K or ATP4 as key candidates for interrupting malaria transmission By Jessica Konijnenburg15/12/201712/01/2018 Categories: Publications Dechering KJ. et al., Sci. Rep. 2017 Dec 15 ABSTRACT Eradication of malaria requires a novel type of drug that blocks transmission from the human to the mosquito…
A potent series targeting the malarial cGMP-dependent protein kinase clears infection and blocks transmission By Jessica Konijnenburg06/09/201712/01/2018 Categories: Publications Baker DA. et al., Nat Commun. 2017 Sep. 5 ABSTRACT To combat drug resistance, new chemical entities are urgently required for use in next generation anti-malarial combinations. We…
Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase. By Jessica Konijnenburg26/04/201701/05/2017 Categories: Publications Paquet T. et al., Sci Transl Med. 2017 Apr 26 ABSTRACT As part of the global effort toward malaria eradication, phenotypic whole-cell screening revealed the 2-aminopyridine class of…
Diversity-oriented synthesis yields novel multistage antimalarial inhibitors. By Monique20/10/201620/04/2017 Categories: Publications Kato N, et. al., Nature. 2016 Oct 20 ABSTRACT Antimalarial drugs have thus far been chiefly derived from two sources-natural products and synthetic drug-like compounds. Here we investigate…
Characterization of Novel Antimalarial Compound ACT-451840: Preclinical Assessment of Activity and Dose-Efficacy Modeling. By Monique04/10/201619/04/2017 Categories: Publications Artemisinin resistance observed in Southeast Asia threatens the continued use of artemisinin-based combination therapy in endemic countries.
An inter-laboratory comparison of standard membrane-feeding assays for evaluation of malaria transmission-blocking vaccines. By Jessica Konijnenburg09/09/201612/01/2018 Categories: Publications Miura K. et al.,Malar J. 2016 Sep 9 ABSTRACT BACKGROUND: An effective malaria transmission-blocking vaccine may play an important role in malaria elimination efforts, and a robust biological…
Analysis of the dose-dependent stage-specific in vitro efficacy of a multi-stage malaria vaccine candidate cocktail. By Jessica Konijnenburg17/05/201612/01/2018 Categories: Publications Boes A. et al., Malar J. 2016 May 17 ABSTRACT BACKGROUND: The high incidence and mortality rate of malaria remains a serious burden for many developing countries, and…
A semi-automated luminescence based standard membrane feeding assay identifies novel small molecules that inhibit transmission of malaria parasites by mosquitoes. By Jessica Konijnenburg21/12/201512/01/2018 Categories: Publications Vos MW. et al., Sci Rep. 2015 Dec 21 ABSTRACT Current first-line treatments for uncomplicated falciparum malaria rapidly clear the asexual stages of the parasite, but do not…
A simple and predictive phenotypic High Content Imaging assay for Plasmodium falciparum mature gametocytes to identify malaria transmission blocking compounds. By Jessica Konijnenburg10/11/201512/01/2018 Categories: Publications Lucantoni L. et al., Sci Rep. 2015 Nov 10 ABSTRACT Plasmodium falciparum gametocytes, specifically the mature stages, are the only malaria parasite stage in humans transmissible to the…
Salinomycin and other ionophores as a new class of antimalarial drugs with transmission-blocking activity. By Jessica Konijnenburg14/09/201512/01/2018 Categories: Publications D’Alessandro S. et al., Antimicrob Agents Chemother. 2015 Sep ABSTRACT The drug target profile proposed by the Medicines for Malaria Venture for a malaria elimination/eradication policy focuses on…
A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria. By Jessica Konijnenburg15/07/201512/01/2018 Categories: Publications Phillips MA et al., Sci Transl Med. 2015 Jul 15 ABSTRACT Malaria is one of the most significant causes of childhood mortality, but disease control efforts are threatened…
Analysis of a Multi-component Multi-stage Malaria Vaccine Candidate–Tackling the Cocktail Challenge. By Jessica Konijnenburg06/07/201512/01/2018 Categories: Publications Boes A, et al., PLoS One. 2015 Jul 6 ABSTRACT Combining key antigens from the different stages of the P. falciparum life cycle in the context of a…
A novel multiple-stage antimalarial agent that inhibits protein synthesis. By Jessica Konijnenburg18/06/201512/01/2018 Categories: Publications Baragaña B et al., Nature. 2015 Jun 18 ABSTRACT There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of…
A combination of new screening assays for prioritization of transmission-blocking antimalarials reveals distinct dynamics of marketed and experimental drugs. By Jessica Konijnenburg19/05/201512/01/2018 Categories: Publications Bolscher JM. et al., J Antimicrob Chemother. 2015 May ABSTRACT OBJECTIVES: The development of drugs to reduce malaria transmission is an important part of malaria eradication plans. We…
Novel pantothenate derivatives for anti-malarial chemotherapy. By Jessica Konijnenburg18/04/201519/04/2017 Categories: Publications Pett HE, Jansen PA, Hermkens PH, Botman PN, Beuckens-Schortinghuis CA, Blaauw RH, Graumans W, van de Vegte-Bolmer M, Koolen KM, Rutjes FP, Dechering KJ, Sauerwein RW, Schalkwijk J….
A scalable assessment of Plasmodium falciparum transmission in the standard membrane-feeding assay, using transgenic parasites expressing green fluorescent protein-luciferase. By Jessica Konijnenburg01/11/201412/01/2018 Categories: Publications Stone WJ. et al., J Infect Dis. 2014 Nov 1 ABSTRACT BACKGROUND: The development of drugs and vaccines to reduce malaria transmission is an important part of eradication…
Targeting Plasmodium PI(4)K to eliminate malaria. By Jessica Konijnenburg01/12/201312/01/2018 Categories: Publications McNamara CW et al., Nature. 2013 Dec 12 ABSTRACT Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we…
A Plasmodium falciparum screening assay for anti-gametocyte drugs based on parasite lactate dehydrogenase detection. By Jessica Konijnenburg19/09/201312/01/2018 Categories: Publications D’Alessandro S. et al., J Antimicrob Chemother. 2013 Sep ABSTRACT OBJECTIVES: Plasmodium gametocytes, responsible for malaria parasite transmission from humans to mosquitoes, represent a crucial target for new antimalarial…
