Article
Multidisciplinary Sciences
Laura E. de Vries, Patrick A. M. Jansen, Catalina Barcelo, Justin Munro, Julie M. J. Verhoef, Charisse Flerida A. Pasaje, Kelly Rubiano, Josefine Striepen, Nada Abla, Luuk Berning, Judith M. Bolscher, Claudia Demarta-Gatsi, Rob W. M. Henderson, Tonnie Huijs, Karin M. J. Koolen, Patrick K. Tumwebaze, Tomas Yeo, Anna C. C. Aguiar, Inigo Angulo-Barturen, Alisje Churchyard, Jake Baum, Benigno Crespo Fernandez, Aline Fuchs, Francisco-Javier Gamo, Rafael V. C. Guido, Maria Belen Jimenez-Diaz, Dhelio B. Pereira, Rosemary Rochford, Camille Roesch, Laura M. Sanz, Graham Trevitt, Benoit Witkowski, Sergio Wittlin, Roland A. Cooper, Philip J. Rosenthal, Robert W. Sauerwein, Joost Schalkwijk, Pedro H. H. Hermkens, Roger Bonnert, Brice Campo, David A. Fidock, Manuel Llinas, Jacquin C. Niles, Taco W. A. Kooij, Koen J. Dechering
Summary: In this study, a pantothenamide, MMV693183, was presented as a first-in-class acetyl-CoA synthetase (AcAS) inhibitor with attractive drug-like properties and in vivo efficacy. The compound showed potent activity against Plasmodium falciparum and Plasmodium vivax, and effectively blocked transmission to Anopheles mosquitoes. These findings make MMV693183 a promising candidate for further clinical development.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Martin A. . Lowe, Alvaro Cardenas, Jean-Pierre Valentin, Zhaoning Zhu, Jan Abendroth, Jose L. Castro, Reiner Class, Annie Delaunois, Renaud Fleurance, Helga Gerets, Vitalina Gryshkova, Lloyd King, Donald D. Lorimer, Malcolm MacCoss, Julian H. Rowley, Marie-Luce Rosseels, Leandro Royer, Richard D. Taylor, Melanie Wong, Oliver Zaccheo, Vishal P. Chavan, Gokul A. . Ghule, Bapusaheb K. Tapkir, Jeremy N. Burrows, Maelle Duffey, Matthias Rottmann, Sergio Wittlin, Inigo Angulo-Barturen, Maria Belen Jimenez-Diaz, Josefine Striepen, Kate J. Fairhurst, Tomas Yeo, David A. . Fidock, Alan F. Cowman, Paola Favuzza, Benigno Crespo-Fernandez, Francisco Javier Gamo, Daniel E. Goldberg, Dominique Soldati-Favre, Benoit Laleu, Teresa de Haro
Summary: This study optimized Plasmepsin X (PMX) and identified potent PMX inhibitors with potential efficacy in treating malaria.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Microbiology
Georges F. R. Radohery, Annabelle Walz, Christin Gumpp, Mohammed H. Cherkaoui-Rbati, Nathalie Gobeau, Jeremy Gower, Miles P. Davenport, Matthias Rottmann, James S. McCarthy, Jorg J. Mohrle, Maria Rebelo, Claudia Demarta-Gatsi, David S. Khoury
Summary: This study investigates the impact of artesunate on the viability of Plasmodium faciparum in humans and mice. The results show that artesunate leads to a faster decline in parasite viability compared to parasitemia. Higher concentrations of artesunate also result in faster parasite elimination. Predictions of infection recrudescence can be accurately made based on measures of parasite viability.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Bini Chhetri Soren, Jagadish Babu Dasari, Alessio Ottaviani, Beatrice Messina, Giada Andreotti, Alice Romeo, Federico Iacovelli, Mattia Falconi, Alessandro Desideri, Paola Fiorani
Summary: A drug obtained from an open-access drug bank was found to strongly and irreversibly inhibit the cleavage step of human DNA topoisomerase IB, reducing cell viability in three different cancer cell lines. Molecular docking and dynamics simulations suggested that the drug binds inside the enzyme's catalytic site, potentially offering a lead compound for developing an efficient anti-tumor molecule targeting human DNA topoisomerase IB.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Marta Andres-Mach, Aleksandra Szewczyk, Miroslaw Zagaja, Joanna Szala-Rycaj, Marta Kinga Lemieszek, Maciej Maj, Michal Abram, Krzysztof Kaminski
Summary: The study discovered that the new compound C11 has a protective effect on astrocytes in vitro and beneficial effects on neurogenesis and cognitive functions in vivo, indicating the need for further research on its neuroprotective mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Jinshi Zhao, C. Skyler Cochrane, Javaria Najeeb, David Gooden, Carly Sciandra, Ping Fan, Nadine Lemaitre, Kate Newns, Robert A. Nicholas, Ziqiang Guan, Joshua T. Thaden, Vance G. G. Fowler Jr, Ivan Spasojevic, Florent Sebbane, Eric J. Toone, Clayton Duncan, Richard Gammans, Pei Zhou
Summary: This article reports the preclinical characterization of a slow, tight-binding LpxC inhibitor, LPC-233, with low picomolar affinity. The compound is a rapid bactericidal antibiotic, unaffected by established resistance mechanisms to commercial antibiotics, and displays outstanding activity against a wide range of Gram-negative clinical isolates in vitro. It is orally bioavailable and efficiently eliminates infections caused by susceptible and multidrug-resistant Gram-negative bacterial pathogens in murine soft tissue, sepsis, and urinary tract infection models.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Chemistry, Medicinal
Dickson Mambwe, Constance M. Korkor, Amanda Mabhula, Zama Ngqumba, Cleavon Cloete, Malkeet Kumar, Paula Ladeia Barros, Meta Leshabane, Dina Coertzen, Dale Taylor, Liezl Gibhard, Mathew Njoroge, Nina Lawrence, Janette Reader, Diogo Rodrigo Moreira, Lyn-Marie Birkholtz, Sergio Wittlin, Timothy J. Egan, Kelly Chibale
Summary: Iterative medicinal chemistry optimization led to the discovery of a highly potent compound 23 with metabolic stability and selectivity, displaying activity against multiple stages of malaria and showing in vivo efficacy in mice.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Betelhem Sirak, Lea Mann, Adrian Richter, Kaleab Asres, Peter Imming
Summary: The leaves of Ranunculus multifidus Forsk. and its major constituent anemonin showed in vivo antimalarial activity against Plasmodium berghei in mice, with RM-H exhibiting superior activity. However, anemonin did not inhibit the growth of Mycobacterium smegmatis and M. abscessus.
Article
Chemistry, Medicinal
A. Dassonville-Klimpt, J. Schneider, C. Damiani, C. Tisnerat, A. Cohen, N. Azas, M. Marchivie, J. Guillon, C. Mullie, P. Agnamey, Anne Totet, J. Dormoi, N. Taudon, B. Pradines, P. Sonnet
Summary: This study designed, synthesized, and evaluated five new series of aminoalcohol quinolines against Pf3D7 and PfW2 strains in vitro. Among the compounds, fourteen showed promising activity with IC50 values below or near 50.0 nM and high selectivity index. Compound 17b exhibited potent antimalarial activity with IC50 values of 14.9 nM and 11.0 nM against Pf3D7 and PfW2, respectively, and a high selectivity index. Further experiments and in vivo studies are needed to confirm its safety and efficacy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Daniel Wang, Caroline E. Porter, Bora Lim, Amanda Rosewell Shaw, Catherine S. Robertson, Mae L. Woods, Ya Xu, Greyson G. W. Biegert, Daisuke Morita, Tao Wang, Bambi J. Grilley, Helen Heslop, Malcolm K. Brenner, Masataka Suzuki
Summary: We have demonstrated the strong antitumor activity of a binary oncolytic/helper-dependent adenovirus (CAdVEC) that lyses tumor cells, expresses IL-12 and PD-L1 blocking antibody. Following successful preclinical studies, we treated four patients with an ultralow dose of CAdVEC, which resulted in significant tumor control and immune repolarization. The combination of CAdVEC with systemic immune checkpoint antibodies induced sustained antitumor responses.
Article
Oncology
Dipranjan Laha, Robert R. C. Grant, Prachi Mishra, Myriem Boufraqech, Min Shen, Ya-Qin Zhang, Matthew D. Hall, Martha Quezado, Michelly Sampaio De Melo, Jaydira Del Rivero, Martha Zeiger, Naris Nilubol
Summary: This preclinical study identified a novel synergistic combination of OTS167 and RGB-286638 in ACC, targeting multiple molecules associated with ACC aggressiveness. Further clinical trials in patients with advanced ACC are warranted.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Kasama Pongsamart, Waree Limwikrant, Uracha Rungsardthong Ruktanonchai, Nattawut Charoenthai, Satit Puttipipatkhachorn
Summary: This study optimized the process conditions for the production of spray-dried powder of dihydroartemisinin (DHA) with beta-cyclodextrin (beta-CD) using a factorial design. The results showed that the inclusion complex formation between DHA and beta-CD improved the dissolution rate of DHA without affecting its antimalarial activity. The spray-dried powder was also found to be chemically and physically stable during storage.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2022)
Article
Engineering, Biomedical
Ripalkumar Shah, Tejal Soni, Unnati Shah, B. N. Suhagia, M. N. Patel, Tejas Patel, Gamal A. Gabr, Bapi Gorain, Prashant Kesharwani
Summary: Lyophilized nanosuspensions of lumefantrine were formulated to improve its low oral bioavailability, showing increased solubility and release rate compared to pure drug. The optimized formulation exhibited stable characteristics and a potential for better malaria control by offering higher release of lumefantrine.
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
(2021)
Article
Public, Environmental & Occupational Health
Francesco De Pretis, Yun Zhou, Pengcheng Xun, Kan Shao
Summary: The BMD methodology is widely used for determining the toxicity value of chemicals, but its application to epidemiological data is limited. This study compares two different methods for BMD analysis in prospective cohort studies on bladder and lung cancer linked to inorganic arsenic exposure, and suggests that modeling adjusted RR values as continuous data for BMD estimation is a more generalizable approach harmonized with the BMD approach using toxicological data.
Article
Biochemical Research Methods
Raghvendra Mall, Abdurrahman Elbasir, Hossam Almeer, Zeyaul Islam, Prasanna R. Kolatkar, Sanjay Chawla, Ehsan Ullah
Summary: A global effort is underway to identify compounds for the treatment of COVID-19, utilizing a machine learning representation framework for compound-viral protein activity prediction and ranking. The consensus framework achieves high Pearson correlation and low mean squared error on an independent test set, identifying potential compounds effective against the SARS-COV-2 virus.
Article
Public, Environmental & Occupational Health
Nicholas M. Douglas, Kim A. Piera, Angela Rumaseb, Benedikt Ley, Nicholas M. Anstey, Ric N. Price
Summary: This article describes a case of severe hemolysis occurring in a G6PD-deficient Australian man after using primaquine for prophylaxis, without malaria. The hemolysis resulted in renal tubular and glomerular injury, and the patient showed elevated levels of urinary beta-2-microglobulin and glycocalyx metabolites. The study also found that regular dose of paracetamol can be safely used in cases of severe oxidative hemolysis.
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(2023)
Article
Public, Environmental & Occupational Health
Kinley Penjor, Ugyen Zangpo, Dorji Tshering, Benedikt Ley, Ric N. Price, Kinley Wangdi
JOURNAL OF TRAVEL MEDICINE
(2023)
Article
Infectious Diseases
Elke Wynberg, Robert J. Commons, Georgina Humphreys, Hazel Ashurst, Rebekah Burrow, George O. Adjei, Martin Adjuik, Nicholas M. Anstey, Anup Anvikar, Kevin J. Baird, Bridget E. Barber, Hubert Barennes, Elisabeth Baudin, David J. Bell, Delia Bethell, Tran Quang Binh, Isabelle Borghini, Cindy S. Chu, Andre Daher, Umberto D'Alessandro, Debashish Das, Timothy Me Davis, Peter J. de Vries, Abdoulaye A. Djimde, Arjen M. Dondorp, Grant Dorsey, Jean-Francois F. Faucher, Carole Fogg, Oumar Gaye, Matthew Grigg, Christoph Hatz, Piet A. Kager, Marcus Lacerda, Moses Laman, Andreas Martensson, Herve Ignace Eby Menan, Wuelton M. Monteiro, Brioni R. Moore, Francois Nosten, Bernhards Ogutu, Lyda Osorio, Louis K. Penali, Dhelio B. Pereira, Awab G. Rahim, Michael Ramharter, Issaka Sagara, Birgit Schramm, Lorenz Seidlein, Andre M. Siqueira, Sodiomon B. Sirima, Peter Starzengruber, Inge Sutanto, Walter R. Taylor, Offianan A. Toure, Jurg Utzinger, Innocent Valea, Giovanni Valentini, Nicholas J. White, Timothy William, Charles J. Woodrow, Caitlin L. Richmond, Philippe J. Guerin, Ric N. Price, Kasia Stepniewska
Summary: This study describes the variability in white blood cell count during acute uncomplicated malaria and estimates the impact of using an assumed value of white blood cell count on estimates of parasite density and clearance.
Article
Infectious Diseases
Annisa Rahmalia, Jeanne Rini Poespoprodjo, Chandra U. R. Landuwulang, Maya Ronse, Enny Kenangalem, Faustina H. H. Burdam, Kamala Thriemer, Angela Devine, Ric N. Price, Koen Peeters Grietens, Benedikt Ley, Charlotte Gryseels
Summary: This study aimed to assess the socio-cultural factors influencing adherence to a 14-day primaquine (PQ) regimen in Papua, Indonesia. The findings show that patients perceived similar severity for two types of malaria (P. vivax and Plasmodium falciparum) and did not differentiate between new infections and relapses. Patients tended to use leftover or over-the-counter drugs for symptom relief, while PQ was considered a supplement rather than a malaria medication. Adherence was lower among highland Papuans, indicating the influence of social and structural barriers.
Article
Public, Environmental & Occupational Health
Fidelis Jacklyn Adella, Moul Vanna, Bipin Adhikari, Sam Ol, Rupam Tripura, Chan Davoeung, James J. Callery, Yok Sovann, Arjun Chandna, Voeunrung Bunreth, Carina Asnong, Lorenz von Seidlein, Arjen M. Dondorp, Richard J. Maude, Yoel Lubell, Bridget Wills, Dysoley Lek, Thomas J. Peto
Summary: This study aimed to assess the feasibility of using point-of-care tests to diagnose acute febrile illnesses in primary care settings. The results showed that all three point-of-care tests performed well under assessment, but sample collection for the dengue test was difficult. Health workers found the diagnostics useful but not as convenient as standard malaria rapid tests.
TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE
(2023)
Review
Microbiology
Arkasha Sadhewa, Sarah Cassidy-Seyoum, Sanjaya Acharya, Angela Devine, Ric N. Price, Muthoni Mwaura, Kamala Thriemer, Benedikt Ley
Summary: Plasmodium vivax malaria continues to be a significant burden in various regions. The use of 8-aminoquinoline drugs is necessary for the complete removal of the parasite, but it can cause severe haemolysis in G6PD deficient patients. The implementation of routine G6PD testing in malaria endemic countries is still lacking, and there are challenges in training healthcare staff, quality control of diagnostics, and communication with affected communities.
Article
Health Care Sciences & Services
Kamala Thriemer, Robert James Commons, Megha Rajasekhar, Tamiru Shibiru Degaga, Krisin Chand, Nguyen Hoang Chau, Ashenafi Assefa, Mohammad Nader Naddim, Ayodhia Pitaloka Pasaribu, Awab Ghulam Rahim, Inge Sutanto, Tran Tinh Hien, Asrat Hailu, Mohammad Anwar Hasanzai, Lenny L. Ekawati, Adugna Woyessa, Tedla Teferi, Naomi Waithira, Walter R. J. Taylor, Benedikt Ley, Arjen Dondorp, J. Kevin Baird, Nicholas J. White, Nicholas P. Day, Ric N. Price, Julie A. Simpson, Lorenz von Seidlein
Summary: This study explored the differences in symptom reporting across multiple trial sites of an antimalarial trial and found significant variations in symptom reporting between different countries. The differences were greater for mild and moderate symptoms compared to severe symptoms.
BMC MEDICAL RESEARCH METHODOLOGY
(2023)
Article
Chemistry, Medicinal
Livio Racane, Lucija Pticek, Sanja Kostrun, Silvana Raic-Malic, Martin Craig Taylor, Michael Delves, Sam Alsford, Francisco Olmo, Amanda Fortes Francisco, John M. Kelly
Summary: We designed and synthesized a series of symmetric benzothiazole derivatives and evaluated their efficacy against Trypanosoma brucei and Plasmodium falciparum. One compound showed high selectivity and trypanocidal activity, curing mice infected with trypanosomiasis. It also exhibited activity against the malaria parasite.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Infectious Diseases
Parinaz Mehdipour, Megha Rajasekhar, Saber Dini, Sophie Zaloumis, Tesfay Abreha, Ishag Adam, Ghulam Rahim Awab, J. Kevin Baird, Larissa W. Brasil, Cindy S. Chu, Liwang Cui, Andre Daher, Margarete Gomes, Lilia Gonzalez-Ceron, Jimee Hwang, Harin Karunajeewa, Marcus V. G. Lacerda, Simone Ladeia-Andrade, Toby Leslie, Benedikt Ley, Kartini Lidia, Alejandro Llanos-Cuentas, Rhea J. Longley, Wuelton Marcelo Monteiro, Dhelio B. Pereira, Komal Raj Rijal, Kavitha Saravu, Inge Sutanto, Walter R. J. Taylor, Pham Vinh Thanh, Kamala Thriemer, Jose Luiz F. Vieira, Nicholas J. White, Lina M. Zuluaga-Idarraga, Philippe J. Guerin, Ric N. Price, Julie A. Simpson, Robert J. Commons, WWARN Vivax Adherence Study Grp
Summary: Reduced adherence increases the risk of P. vivax recurrence.
Article
Infectious Diseases
C. R. Walker, R. I. Hickson, E. Chang, P. Ngor, S. Sovannaroth, J. A. Simpson, D. J. Price, J. M. McCaw, R. N. Price, J. A. Flegg, A. Devine
Summary: Plasmodium falciparum and P. vivax are the two most common causes of malaria, with P. vivax posing a greater challenge to eliminating malaria due to its ability to cause relapsing episodes. Mixed infections of both species can complicate treatment and detection. A stochastic mathematical model was used to assess different treatment strategies, and it was found that a unified radical cure strategy and mass drug administration with schizonticidal treatment were effective in reducing malaria cases and deaths.
Article
Infectious Diseases
Wondimagegn Adissu, Marcelo Brito, Eduardo Garbin, Marcela Macedo, Wuelton Monteiro, Sandip Kumar Mukherjee, Jane Myburg, Mohammad Shafiul Alam, Germana Bancone, Pooja Bansil, Sampa Pal, Abhijit Sharma, Stephanie Zobrist, Andrew Bryan, Cindy S. Chu, Santasabuj Das, Gonzalo J. Domingo, Amanda Hann, James Kublin, Marcus V. G. Lacerda, Mark Layton, Benedikt Ley, Sean C. Murphy, Francois Nosten, Dhelio Pereira, Ric N. Price, Arunansu Talukdar, Daniel Yilma, Emily Gerth-Guyette
Summary: The study pooled data from clinical studies conducted in different countries to evaluate the performance of the STANDARD G6PD Test. The test showed high sensitivity and specificity in capillary and venous specimens, making it a reliable tool to guide the treatment of antimalarial drugs.
PLOS NEGLECTED TROPICAL DISEASES
(2023)
Article
Infectious Diseases
Walter R. J. Taylor, Niamh Meagher, Benedikt Ley, Kamala Thriemer, Germana Bancone, Ari Satyagraha, Ashenafi Assefa, Krisin Chand, Nguyen Hoang Chau, Mehul Dhorda, Tamiru S. Degaga, Lenny L. Ekawati, Asrat Hailu, Mohammad Anwar Hasanzai, Mohammad Nader Naddim, Ayodhia Pitaloka Pasaribu, Awab Ghulam Rahim, Inge Sutanto, Ngo Viet Thanh, Nguyen Thi Tuyet-Trinh, Naomi Waithira, Adugna Woyessa, Arjen Dondorp, Lorenz von Seidlein, Julie A. Simpson, Nicholas J. White, J. Kevin Baird, Nicholas P. Day, Ric N. Price
Summary: This study focuses on the observational study of primaquine in patients with Plasmodium vivax malaria, and finds that a weekly dose of primaquine (PQ8W) is highly effective in preventing recurrence.
PLOS NEGLECTED TROPICAL DISEASES
(2023)
Article
Chemistry, Medicinal
Dawson B. Ling, William Nguyen, Oliver Looker, Zahra Razook, Kirsty Mccann, Alyssa E. Barry, Christian Scheurer, Sergio Wittlin, Mufuliat Toyin Famodimu, Michael J. Delves, Hayley E. Bullen, Brendan S. Crabb, Brad E. Sleebs, Paul R. Gilson
Summary: In this study, a low micromolar inhibitor was discovered after screening 250 compounds against the deadly malarial parasite Plasmodium falciparum. The inhibitor showed potent activity against parasite growth and red blood cell invasion. Further optimization of the compound led to a 250-fold increase in potency against parasite blood-stage growth, and it was found that the target of the compound is the phosphatidylinositol kinase PfPI4KIIIB.
ACS INFECTIOUS DISEASES
(2023)
Article
Hematology
Steven Kho, Nurjati C. Siregar, Labibah Qotrunnada, Aurelie Fricot, Abdoulaye Sissoko, Putu A. I. Shanti, Freis Candrawati, Noy N. Kambuaya, Hasrini Rini, Benediktus Andries, David Hardy, Nur I. Margyaningsih, Fauziyah Fadllan, Desandra A. Rahmayenti, Agatha M. Puspitasari, Leo Leonardo, Bagus T. G. Yayang, Dewi S. Margayani, Pak Prayoga, Leily Trianty, Enny Kenangalem, Ric N. Price, Tsin W. Yeo, Gabriela Minigo, Rintis Noviyanti, Jeanne R. Poespoprodjo, Nicholas M. Anstey, Pierre A. Buffet
Summary: Splenomegaly in malaria patients is associated with retention of uninfected red blood cells in the spleen, which is the major mechanism of anemia.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Review
Public, Environmental & Occupational Health
Holger W. Unger, Sanjaya Acharya, Lachlan Arnold, Connie Wu, Anna Maria van Eijk, Georgia R. Gore-Langton, Feiko O. ter Kuile, Elvin Lufele, R. Matthew Chico, Ric N. Price, Brioni R. Moore, Kamala Thriemer, Stephen J. Rogerson
Summary: Half of all pregnancies at risk of malaria occur in the Asia-Pacific region, where the co-existence of Plasmodium falciparum and Plasmodium vivax is common. Malaria control in pregnancy faces challenges due to high-grade antimalarial resistance and the need for more sensitive diagnostic tests. A more systematic approach is needed to prevent malaria in pregnancy in the Asia-Pacific region.
LANCET GLOBAL HEALTH
(2023)