Article
Multidisciplinary Sciences
Arne Alder, Cecilia P. Sanchez, Matthew R. G. Russell, Lucy M. Collinson, Michael Lanzer, Michael J. Blackman, Tim-Wolf Gilberger, Joachim M. Matz
Summary: Malaria parasites use a complex to acidify the digestive vacuole and degrade host erythrocyte hemoglobin, which is essential for their survival in the human bloodstream.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Michele S. Y. Tan, Konstantinos Koussis, Chrislaine Withers-Martinez, Steven A. Howell, James A. Thomas, Fiona Hackett, Ellen Knuepfer, Min Shen, Matthew D. Hall, Ambrosius P. Snijders, Michael J. Blackman
Summary: The study reveals the pathway of malaria parasite egress from host erythrocytes and identifies SERA6 as a target for a new class of antimalarial drugs. Activation of SERA6 involves an autocatalytic step triggered by SUB1 cleavage, which requires interaction with the protein cofactor MSA180 for autoproteolytic maturation.
Article
Plant Sciences
Gervais Mouthe Happi, Pamela Kemda Nangmo, Liliane Clotide Dzouemo, Sorelle Fotsing Kache, Ariane Dolly Kenmogne Kouam, Jean Duplex Wansi
Summary: Meliaceae plants are important herbal sources for treating malaria in traditional African medicine. Studies have found significant antiplasmodial and insecticidal activities in this plant family, suggesting their potential as eco-friendly pesticides.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Immunology
Sungano Mharakurwa, Zvifadzo Matsena-Zingoni, Nobert Mudare, Charmaine Matimba, Tanatswa Xuxa Gara, Aramu Makuwaza, Gladys Maponga, Shungu Munyati, Lovemore Gwanzura, Susan L. Mutambu, Peter Mason, Tamaki Kobayashi, Nicholas Midzi, William J. Moss, Matthew M. Ippolito
Summary: The removal of chloroquine from national malaria formularies can lead to a decrease in chloroquine-resistant Plasmodium falciparum, highlighting the significant impact of drug policy on antimalarial resistance in malaria control programs.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Multidisciplinary Sciences
Elina Lidumniece, Chrislaine Withers-Martinez, Fiona Hackett, Christine R. Collins, Abigail J. Perrin, Konstantinos Koussis, Claudine Bisson, Michael J. Blackman, Aigars Jirgensons
Summary: Malaria is a devastating infectious disease causing over 400,000 deaths annually. Researchers have developed substrate-based peptidic boronic acids that inhibit a parasite protease called SUB1, preventing parasite replication through egress and potentially serving as a new class of antimalarial drugs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Roberta Ettari, Santo Previti, Carla Di Chio, Maria Zappala
Summary: Malaria is a serious global public health issue, with chemotherapy being the only current treatment method due to lack of effective vaccine. However, the resistance to antimalarial drugs poses a challenge to the current therapeutic regimen. Therefore, the search for new drug targets is a pressing priority.
CURRENT MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Jeevan Patra, Devika Rana, Smriti Arora, Mintu Pal, Neeraj Mahindroo
Summary: Malaria, a tropical disease caused by Plasmodium species, has a significant burden on human health in various parts of the world. However, the effectiveness of current chemotherapeutic drugs and combination therapies against the pathogenic Plasmodium species is decreasing due to drug resistance. Therefore, there is a need to identify new drug targets and chemical compounds to combat malaria. Falcipains, cysteine proteases involved in heme metabolism, have been identified as potential drug targets for the treatment of Plasmodium species. This perspective discusses the biology, biochemistry, structure, and genetics of falcipains, as well as efforts to design novel compounds targeting falcipains for antimalarial activity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Immunology
Biraj Shrestha, Zalak Shah, Andrew P. Morgan, Piyaporn Saingam, Chaiyaporn Chaisatit, Suwanna Chaorattanakawee, Chantida Praditpol, Nonlawat Boonyalai, Paphavee Lertsethtakarn, Mariusz Wojnarski, Molly Deutsch-Feldman, Matthew Adams, Darapiseth Sea, Soklyda Chann, Stuart D. Tyner, Charlotte A. Lanteri, Michele D. Spring, David L. Saunders, Philip L. Smith, Chanthap Lon, Panita Gosi, Somethy Sok, Prom Satharath, Huy Rekol, Dysoley Lek, Brian A. Vesely, Jessica T. Lin, Norman C. Waters, Shannon Takala-Harrison
Summary: This study estimated the prevalence of piperaquine resistance mutations in Plasmodium falciparum isolates collected in northern Cambodia from 2009 to 2017. The results showed a significant increase in newly emerged PfCRT mutations after the change to dihydroartemisinin-piperaquine in 2010, with a decline in PfCRT F145I prevalence after 2014. Additionally, there was a decrease in parasites with amplified pfpm2 after the switch to artesunate-mefloquine.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Medicine, General & Internal
Melissa D. Conrad, Victor Asua, Shreeya Garg, David Giesbrecht, Karamoko Niare, Sawyer Smith, Jane F. Namuganga, Thomas Katairo, Jennifer Legac, Rebecca M. Crudale, Patrick K. Tumwebaze, Samuel L. Nsobya, Roland A. Cooper, Moses R. Kamya, Grant Dorsey, Jeffrey A. Bailey, Philip J. Rosenthal
Summary: This study identified multifocal emergence and spread of Plasmodium falciparum with partial resistance to artemisinins in Uganda. The emergence and spread of resistance were predominantly observed in areas where effective malaria control had been discontinued or transmission was unstable.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Vinay Shankar Tiwari, Prince Joshi, Kanchan Yadav, Anamika Sharma, Sushobhan Chowdhury, Ashan Manhas, Niti Kumar, Renu Tripathi, Wahajul Haq
Summary: A series of novel 4-aminoquinoline analogues with a methyl group were synthesized and evaluated for their antimalarial activity, showing good potential in inhibiting Plasmodium falciparum with low toxicity levels. The introduction of a 4-methylamino substitution is well tolerated and holds promise for the discovery of new antimalarial agents against drug-resistant malaria.
Article
Multidisciplinary Sciences
Brendan Fries, Carlos A. Guerra, Guillermo A. Garcia, Sean L. Wu, Jordan M. Smith, Jeremias Nzamio Mba Oyono, Olivier T. Donfack, Jose Osa Osa Nfumu, Simon Hay, David L. Smith, Andrew J. Dolgert
Summary: Different population layers performed differently in matching the gold standard distribution at different population densities. Choosing the appropriate population map has a significant impact on burden estimates in a malaria model.
Article
Multidisciplinary Sciences
Theresa Reiker, Monica Golumbeanu, Andrew Shattock, Lydia Burgert, Thomas A. Smith, Sarah Filippi, Ewan Cameron, Melissa A. Penny
Summary: Individual-based models are essential in the global fight against infectious diseases, but the complexity of the models can pose challenges for calibration. The authors propose using a Bayesian optimization framework to calibrate a complex malaria transmission simulator, resulting in improved fitting outcomes compared to previous calibrations.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Nicola Relitti, Stefano Federico, Luca Pozzetti, Stefania Butini, Stefania Lamponi, Donatella Taramelli, Sarah D'Alessandro, Rowena E. Martin, Sarah H. Shafik, Robert L. Summers, Simone K. Babij, Annette Habluetzel, Sofia Tapanelli, Reto Caldelari, Sandra Gemma, Giuseppe Campiani
Summary: Resistance to common malaria therapies remains a significant concern worldwide. Research has shown that certain compounds can partially resensitize chloroquine-resistant strains of Plasmodium falciparum, and new analogues have demonstrated good cytotoxicity against the parasite, with potential inhibitory effects on the PfCRT-mediated transport of chloroquine.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
James A. Watson, Sophie Uyoga, Perpetual Wanjiku, Johnstone Makale, Gideon M. Nyutu, Neema Mturi, Elizabeth C. George, Charles J. Woodrow, Nicholas P. J. Day, Philip Bejon, Robert O. Opoka, Arjen M. Dondorp, Chandy C. John, Kathryn Maitland, Thomas N. Williams, Nicholas J. White
Summary: Severe malaria caused by Plasmodium falciparum is difficult to accurately diagnose in children in high-transmission settings. A combination of platelet count and plasma PfHRP2 concentration can be used to identify severe falciparum malaria in severely ill patients. About one-third of children enrolled in clinical studies of severe malaria in high-transmission settings in Africa had other causes of their severe illness.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Microbiology
Jan Stephan Wichers-Misterek, Annika M. Binder, Paolo Mesen-Ramirez, Lilian Patrick Dorner, Soraya Safavi, Gwendolin Fuchs, Tobias L. Lenz, Anna Bachmann, Danny Wilson, Friedrich Frischknecht, Tim-Wolf Gilberger
Summary: The unique three-membrane pellicle is a key feature driving the transition between different life cycle stages of the malaria parasite. A novel subpellicular microtubule-associated protein, SPM3, was identified in the genus Plasmodium. Knockout of this protein resulted in malformed gametocytes and aberrant microtubules in Plasmodium falciparum, while in Plasmodium berghei, it caused perturbed microtubule architecture, aberrant sporozoite motility, and decreased transmission efficiency.
Article
Multidisciplinary Sciences
Sherwin Chan, Jun-Hong Ch'ng, Mats Wahlgren, Jessada Thutkawkorapin
SCIENTIFIC REPORTS
(2017)
Article
Chemistry, Multidisciplinary
Jing Li, Martin J. Lear, Yujiro Hayashi
CHEMICAL COMMUNICATIONS
(2018)
Article
Multidisciplinary Sciences
Maria del Pilar Quintana, Jun-Hong Ch'ng, Kirsten Moll, Arash Zandian, Peter Nilsson, Zulkarnain Md Idris, Somporn Saiwaew, Ulrika Qundos, Mats Wahlgren
SCIENTIFIC REPORTS
(2018)
Article
Multidisciplinary Sciences
Maria del Pilar Quintana, Jun-Hong Ch'ng, Arash Zandian, Maryam Imam, Kjell Hultenby, Michael Theisen, Peter Nilsson, Ulrika Qundos, Kirsten Moll, Sherwin Chan, Mats Wahlgren
Review
Microbiology
Jun-Hong Ch'ng, Kelvin K. L. Chong, Ling Ning Lam, Jun Jie Wong, Kimberly A. Kline
NATURE REVIEWS MICROBIOLOGY
(2019)
Correction
Microbiology
Jun-Hong Ch'ng, Kelvin K. L. Chong, Ling Ning Lam, Jun Jie Wong, Kimberly A. Kline
NATURE REVIEWS MICROBIOLOGY
(2019)
Article
Biotechnology & Applied Microbiology
Martin J. Lear, Keiichiro Hirai, Kouki Ogawa, Shuji Yamashita, Masahiro Hirama
JOURNAL OF ANTIBIOTICS
(2019)
Article
Chemistry, Multidisciplinary
Jing Li, Martin J. Lear, Yujiro Hayashi
Summary: A new transition metal-free synthesis method for cyclopropanes has been achieved, which tolerates various aryl systems, as well as sulfide or alkene functionality, to yield cis-aryl/cyano cyclopropanes bearing congested tetrasubstituted quaternary carbons.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Organic
Subramanian G. Gramani, Ravi K. Sriramula, Karthik Sekar, Eugene G. Yang, Praveena Battu, Aicha Kopecky, Martin J. Lear
Summary: This study presents a concise and (Z)-selective approach to the synthesis of the 14-membered carbocycle of bielschowskysin using naturally occurring chiral starting materials. By employing cyclic diol benzylidene protection, the issues of steric hindrance and alkyne chelation of the ruthenium catalyst in the synthesis process were effectively overcome.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Jing Li, Eunsang Kwon, Martin J. Lear, Yujiro Hayashi
Summary: In halogen chemistry, the reaction between amines and N-halosuccinimides is complex, with NIS mainly forming non-covalent halogen bonded amine complexes and similar behavior observed for NBS, requiring catalysis with an appropriate Brønsted acid.
HELVETICA CHIMICA ACTA
(2021)
Article
Multidisciplinary Sciences
Jun-Hong Ch'ng, Kirsten Moll, Katja Wyss, Ulf Hammar, Mikael Ryden, Olle Kampe, Anna Farnert, Mats Wahlgren
Summary: The study reveals an association between type 2 diabetes and parasite growth and rosetting, potentially explaining the protective effect of good glycemic control against severe malaria in subjects with diabetes.
Article
Ecology
Jun-Hong Ch'ng, Mugil Muthu, Kelvin K. L. Chong, Jun Jie Wong, Casandra A. Z. Tan, Zachary J. S. Koh, Daniel Lopez, Artur Matysik, Zeus J. Nair, Timothy Barkham, Yulan Wang, Kimberly A. Kline
Summary: This study reports the enhanced biofilm biomass resulting from the combination of Staphylococcus aureus and Enterococcus faecalis, which is dependent on the activation of E. faecalis aerobic respiration. S. aureus provides heme to activate E. faecalis respiration, and E. faecalis gelatinase activity facilitates heme extraction. This interspecies interaction and metabolic cross-feeding may explain the frequent co-occurrence of these microbes in biofilm-associated infections.
Article
Chemistry, Organic
Shoji Kobayashi, Ryo Yamaguchi, Fumiya Yamamoto, Jun Komori, Hotaka Sakamoto, Takahiro Kasashima, Louis Adriaenssens, Martin J. Lear
Summary: An economic and scalable one-pot procedure for converting benzylic or aliphatic alcohols to various N-functionalized amines is reported. The method involves oxidative formation of acid chloride intermediates and the Curtius rearrangement of acyl azides, leading to overall yields of 38-83%. The use of a green solvent and minimal amounts of chlorinating agent contribute to the economic and environmentally friendly nature of the process.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Xiaonan Wang, Silong Xu, Yuhai Tang, Martin J. J. Lear, Wangxiao He, Jing Li
Summary: The replacement of oxoamide units with thioamides is an effective strategy to enhance biological activity and resistance to enzymatic degradation in peptide therapeutics. This study presents a direct coupling method using readily available nitroalkanes and amines with elemental sulfur and base to form thioamides and thiopeptides. The developed method allows for selective and stereo-retentive introduction of thioamide bonds into peptide or protein backbones, enabling the synthesis of diverse thioamides in high yields.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Xin He, Pengchen Ma, Yuhai Tang, Jing Li, Shenyu Shen, Martin J. Lear, K. N. Houk, Silong Xu
Summary: We report a phosphine-catalyzed (3 + 2) annulation of cyclopropenones with various electrophilic pi systems, yielding products including butenolides, butyrolactams, maleimides, and iminomaleimides in high yields with a wide range of substrates. An alpha-ketenyl phosphorous ylide is identified as the key intermediate, which undergoes preferential catalytic cyclization with aldehydes. This phosphine-catalyzed activation of cyclopropenones provides a versatile C-3 synthon for formal cycloadditon reactions.