Review
Cell Biology
Melissa Louise Stofberg, Celine Caillet, Marianne de Villiers, Tawanda Zininga
Summary: Malaria remains a major killer parasitic disease in tropical settings, with the development of antimalarial drug resistance posing a significant challenge in disease control. Therefore, there is a need to explore new strategies and treatment options to reverse the development of antimalarial drug resistance.
Article
Immunology
DeAnna J. Friedman-Klabanoff, Mark A. Travassos, Olukemi O. Ifeonu, Sonia Agrawal, Amed Ouattara, Andrew Pike, Jason A. Bailey, Matthew Adams, Drissa Coulibaly, Kirsten E. Lyke, Matthew B. Laurens, Shannon Takala-Harrison, Bourema Kouriba, Abdoulaye K. Kone, Ogobara K. Doumbo, Jigar J. Patel, Mahamadou A. Thera, Philip L. Felgner, John C. Tan, Christopher Plowe, Andrea A. Berry
Summary: In a study conducted in Mali, it was found that adults had stronger antibody responses to circumsporozoite protein (CSP) compared to children, and responded to more variants near the central repeat region. Children acquired short-lived immunity to an epitope proximal to the central repeat region, but not to the central repeat region itself. This approach has the potential to differentiate immunodominant from protective epitope-specific responses when combined with longitudinal infection data.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Chemistry, Physical
Ugwu D. Izuchukwu, Fredrick C. Asogwa, Hitler Louis, Eze F. Uchenna, Terkumbur E. Gber, Ugwu M. Chinasa, Ndefo J. Chinedum, Benedeth O. Eze, Adedapo S. Adeyinka, Okoro U. Chris
Summary: Zinc chloride mediated synthesis, DFT studies and molecular docking were done on new carboxamide derivatives containing sulphonamide functionality. The results showed that certain derivatives could be better anti-malaria drug candidates compared to others, based on binding affinities obtained from docking scores.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Infectious Diseases
Sangdao Somsri, Mathirut Mungthin, Natthaporn Klubthawee, Poom Adisakwattana, Warunee Hanpithakpong, Ratchaneewan Aunpad
Summary: Mitochondria are considered a novel drug target due to their key role in energy production and programmed cell death. A mitochondria-penetrating peptide, (F(x)r)(3), showed potent and selective antimalarial activity by entering malaria-infected red cells and targeting the parasite mitochondria without significant toxicity to mammalian cells. This study provides a first report on the antimalarial activity of (F(x)r)(3) and its rapid killing activity compared to the known drug atovaquone.
Review
Biochemistry & Molecular Biology
Tanima Dutta, Harpreet Singh, Adrienne L. Edkins, Gregory L. Blatch
Summary: Heat shock protein 90 (Hsp90) plays an important role in cellular protein homeostasis. In parasitic protozoans, such as Plasmodium falciparum, Hsp90 and its associated co-chaperones have unique properties and functions. Understanding these differences may lead to the development of drugs to combat malaria.
Article
Biochemistry & Molecular Biology
James H. Zothantluanga, Abd. Kakhar Umar, Keerthic Aswin, Sanchaita Rajkhowa, Dipak Chetia
Summary: In this study, in-silico techniques were used to predict the molecular drug targets of luteolin against Plasmodium falciparum. The results showed that luteolin outperformed the native ligands in molecular docking and MD simulations, but only outperformed the native ligand of PfDHFR-TS in MM-GBSA calculations. Among the studied proteins, PfDHFR-TS was predicted as the most favorable drug target for luteolin.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
So Yeon Cho, Hye-Won Na, Han Byeol Oh, Yun Mi Kwak, Wan Seok Song, Sun Cheol Park, Wook-Jong Jeon, Hongbaek Cho, Byung-Chul Oh, Jeongho Park, Seung Goo Kang, Geun-Shik Lee, Sung-Il Yoon
Summary: The pathogenic bacterium Listeria monocytogenes regulates flagellar expression using the GmaR-MogR system, which is temperature-dependent. At low temperatures, GmaR binds to MogR and inhibits flagellar expression. However, at high temperatures, GmaR forms aggregates and loses its ability to neutralize MogR.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Physical
Saroj Kumar Panda, Shalini Saxena, Parth Sarthi Sen Gupta, Malay Kumar Rana
Summary: Malaria is a life-threatening disease caused by Plasmodium parasites and has posed a significant health challenge globally due to antimalarial resistance. Discovering effective new antimalarial medicines is crucial to combat resistance to current therapies. In this study, a protease called Plasmepsin X (PMX) was identified as playing a key role in the invasion of parasites, leading to the identification of potential inhibitors through structure-based pharmacophore generation and virtual screening. These new inhibitors show promise for further in vivo studies as antimalarial drugs.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Biochemistry & Molecular Biology
Anna Jaromin, Beata Gryzlo, Marek Jamrozik, Silvia Parapini, Nicoletta Basilico, Marek Cegla, Donatella Taramelli, Agnieszka Zagorska
Summary: Malaria remains a major threat with drug resistance on the rise. New tetrahydro-beta-carbolines were synthesized and tested for antiplasmodial activity, with N-(3,3-dimethylbutyl)-1-octyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b] indole-3-carboxamide (7) showing the most promising results. Further research is being conducted on its potential mechanisms of action and delivery systems.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Xin Ji, Zhensheng Wang, Qianqian Chen, Jingzhong Li, Heng Wang, Zenglei Wang, Lan Yang
Summary: The study utilized virtual screening based on PMV structure, identifying four compounds that showed promising inhibition of parasite growth and strong binding activities with the PfPMV model. Experimental validation highlighted the potential of one compound to be developed as an active PfPMV inhibitor with minimal impact on normal cell viability.
Article
Biochemical Research Methods
Ashis Kumar Goswami, Hemanta Kumar Sharma, Neelutpal Gogoi, Ankita Kashyap, Bhaskar Jyoti Gogoi
Summary: The study evaluated the antimalarial activity of methanol extracts of Coptis teeta in vitro and identified noroxyhydrastinine as a potential antimalarial agent through in silico analysis. Noroxyhydrastinine showed better binding affinity in comparison to chloroquine and demonstrated stability in the binding pocket of dihydroorotate dehydrogenase. The findings suggest noroxyhydrastinine as a promising candidate for further development as an antimalarial drug.
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
(2022)
Article
Biochemistry & Molecular Biology
Hemlata Pundir, Manish Pant, Tanuja Joshi, Sunaullah Bhat, Ramanand Pathak, Atal Bihari Bajpai, Subhash Chandra, Sushma Tamta
Summary: This study identifies two plant compounds, Alpha-cyperone and Humulene oxide, which can bind to the malaria parasite's vector protein OBP4 and exhibit strong affinities and high stability. These compounds also show safe and suitable properties for the development of natural repellents.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
David Bacelar Costa Junior, Janay Stefany Carneiro Araujo, Larissa de Mattos Oliveira, Flavio Simas Moreira Neri, Paulo Otavio Lourenco Moreira, Alex Gutterres Taranto, Amanda Luisa Fonseca, Fernando de Pilla Varotti, Franco Henrique Andrade Leite
Summary: Malaria, caused by Plasmodium spp., remains a significant public health issue with drug resistance limiting chemotherapy. By exploring essential therapeutic targets of the parasite, a potential new antimalarial molecule with activity comparable to artemether was identified through virtual screening. This molecule, previously used in traditional Chinese medicine, may offer a repurposing opportunity to expedite drug development. Molecular dynamics studies confirmed the stability of molecular interactions, paving the way for further research on new derivatives for in vitro and in vivo evaluation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Environmental Sciences
Chinnaperumal Kamaraj, Chinnasamy Ragavendran, R. C. Satish Kumar, Sarvesh Sabarathinam, Cittrarasu Vetrivel, Mariyappan Vaithiyalingam, Guilherme Malafaia
Summary: This study focused on the synthesis of palladium nanoparticles from macroalgae for potential anti-malarial activity and cytotoxicity assessment. The nanoparticles showed high inhibitory effects against Plasmodium falciparum and low toxicity to HeLa cells. These promising results support the application of bionanotechnology for malaria control.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Article
Biochemistry & Molecular Biology
Abeer H. Elmaidomy, Eman Maher Zahran, Raya Soltane, Ahlam Alasiri, Hani Saber, Che Julius Ngwa, Gabriele Pradel, Faisal Alsenani, Ahmed M. Sayed, Usama Ramadan Abdelmohsen
Summary: Compound 2 from the green seaweed Halimeda macroloba exhibits potential antimalarial activity and strongly binds to cytochrome-C enzyme, making it a promising lead compound for the development of new antimalarial agents.
Article
Biochemistry & Molecular Biology
Amaravadhi Harikishore, Wuan-Geok Saw, Priya Ragunathan, Dennis Litty, Thomas Dick, Volker Mueller, Gerhard Gruber
Summary: This study elucidated the differences in the amino acid composition and structural features of the mycobacterial F-ATP synthase compared to other counterparts, paving the way for discovering molecules that can interfere with the regulative mechanisms of this essential energy converter. The essentiality of the mycobacterial peripheral stalk subunit delta for effective catalysis was demonstrated, leading to the identification of a potent subunit delta inhibitor. Targeting the delta subunit shows potential for developing F-ATP synthase inhibitors.
ACS CHEMICAL BIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Wei-Wen Lim, Jinrui Dong, Benjamin Ng, Anissa A. Widjaja, Chen Xie, Liping Su, Xiu-Yi Kwek, Nicole G. Z. Tee, Chee Jian Pua, Sebastian Schafer, Sivakumar Viswanathan, Stuart A. Cook
Summary: IL11 is upregulated in the aorta of Marfan syndrome patients, leading to aortic dilatation, inflammation, and fibrosis. Therapeutic inhibition of IL11 may be a new approach in treating Marfan syndrome.
CIRCULATION RESEARCH
(2022)
Article
Urology & Nephrology
Anissa A. Widjaja, Shamini G. Shekeran, Eleonora Adami, Joyce G. Wei Ting, Jessie Tan, Sivakumar Viswanathan, Sze Yun Lim, Puay Hoon Tan, Norbert Huebner, Thomas Coffman, Stuart A. Cook
Summary: This study demonstrates that neutralizing IL-11 antibody can reduce fibrosis, inflammation, and epithelial-to-mesenchymal transition while improving renal function in an Alport syndrome mouse model. Combined with ACE inhibition, anti-IL-11 therapy can synergistically extend lifespan. These findings suggest that targeting IL-11 holds promise for treating progressive kidney disease in Alport syndrome.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Joon Shin, Amaravadhi Harikishore, Chui Fann Wong, Priya Ragunathan, Thomas Dick, Gerhard Gruber
Summary: Mycobacterium abscessus (Mab) is a clinically relevant nontuberculous mycobacterium that is intrinsically multi-drug-resistant, causing difficult-to-cure lung disease. Structural and dynamic studies of the Mab epsilon subunit reveal insights into the coupling process within the protein, highlighting the potential for development of novel antimycobacterial compounds. Evaluation of the inhibitor Ep1MabF1 demonstrates its effectiveness in inhibiting Mab growth and bacterial ATP synthesis.
Article
Biochemistry & Molecular Biology
Anissa A. Widjaja, Sonia Chothani, Sivakumar Viswanathan, Joyce Wei Ting Goh, Wei-Wen Lim, Stuart A. Cook
Summary: IL11 is pro-inflammatory in fibroblasts by activating the signaling pathways and promoting transcriptional responses related to inflammation, leading to the upregulation of various inflammatory factors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jinrui Dong, Wei-Wen Lim, Shamini G. Shekeran, Jessie Tan, Sze Yun Lim, Joyce Wei Ting Goh, Benjamin L. George, Sebastian Schafer, Stuart A. Cook, Anissa A. Widjaja
Summary: This study investigated the role of IL11 and gp130 in APAP-induced liver injury using mouse models with conditional knockout of Il11 or gp130 in hepatocytes. The results showed that IL11/gp130 signaling contributes to liver damage and inhibits regeneration in APAP toxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Wuan-Geok Saw, Chen Yen Leow, Amaravadhi Harikishore, Joon Shin, Malcolm S. Cole, Wassihun Wedajo Aragaw, Priya Ragunathan, Pooja Hegde, Courtney C. Aldrich, Thomas Dick, Gerhard Grueber
Summary: This study investigated the structure-function relationship of PanD in Mycobacterium abscessus (Mab), a non-tuberculous mycobacterial lung pathogen, and compared it to Mycobacterium tuberculosis (Mtb) PanD. The solution structure of Mab PanD was determined using solution X-ray scattering data, revealing the orientation of the C-termini relative to the catalytic core. Enzymatic and mutational analyses identified critical residues involved in substrate tunnel and enzymatic activity. A potent inhibitor of Mab PanD was discovered using a library of POA analogues. Unlike PZA and POA, this inhibitor showed significant antibacterial activity against different subspecies of Mab.
ACS INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Pooja V. Hegde, Wassihun W. Aragaw, Malcolm S. Cole, Gorakhnath Jachak, Priya Ragunathan, Sachin Sharma, Amaravadhi Harikishore, Gerhard Gruber, Thomas Dick, Courtney C. Aldrich
Summary: Tuberculosis (TB) is a major cause of infectious disease-related mortality and morbidity. Pyrazinamide (PZA) is a crucial component of TB treatment, but its mechanism of action is still unclear. Recent research has shown that the active metabolite pyrazinoic acid (POA) induces targeted protein degradation of the enzyme PanD in Mycobacterium tuberculosis (Mtb). By designing POA analogs, researchers have made progress in improving potency and overcoming PZA resistance.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Anissa A. Widjaja, Sivakumar Viswanathan, Shamini G. Shekeran, Eleonora Adami, Wei-Wen Lim, Sonia Chothani, Jessie Tan, Joyce Wei Ting Goh, Hui Mei Chen, Sze Yun Lim, Carine M. Boustany-Kari, Julie Hawkins, Enrico Petretto, Norbert Huebner, Sebastian Schafer, Thomas M. Coffman, Stuart A. Cook
Summary: In severe kidney disease, inhibiting IL11 can restore kidney function and reverse tissue damage through promoting regeneration.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Vikneswaran Mathiyazakan, Chui-Fann Wong, Amaravadhi Harikishore, Kevin Pethe, Gerhard Gruber
Summary: The Mycobacterial cytochrome bcc:aa(3) complex is a supercomplex that combines three cytochrome oxidases into one machine, which performs electron transfer and proton transport for ATP synthesis. It is a valid drug target for Mycobacterium tuberculosis infections.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Review
Pharmacology & Pharmacy
Amaravadhi Harikishore, Vikneswaran Mathiyazakan, Kevin Pethe, Gerhard Gruber
Summary: This review discusses the structure and mechanism of Mtb's respiratory chain complex, cytochrome bd oxidase, as well as its features in structure-activity relationship. It emphasizes the importance of a deeper understanding of the structure and mechanism of Mtb's cytochrome bd oxidase for drug development.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Editorial Material
Pathology
Anissa A. Widjaja, Stuart A. Cook
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Ranit Pariary, Sandip Dolui, Gourav Shome, Sk Abdul Mohid, Achintya Saha, Bhisma N. Ratha, Amaravadhi Harikishore, Kuladip Jana, Atin K. Mandal, Anirban Bhunia, Nakul C. Maiti
Summary: Our studies demonstrate that Coomassie Brilliant Blue G-250 shows promise as a chemical chaperone for stabilising the alpha-helical native human insulin conformers, preventing their aggregation and increasing insulin secretion. This multipolar effect, along with its non-toxic nature, could be valuable for the development of highly bioactive, targeted, and biostable therapeutic insulin.
CHEMICAL COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Mark Sweeney, Katie O'Fee, Chelsie Villanueva-Hayes, Ekhlas Rahman, Michael Lee, Konstantinos Vanezis, Ivan Andrew, Wei-Wen Lim, Anissa Widjaja, Paul J. R. Barton, Stuart A. Cook
Summary: This study demonstrates that IL11 expression in cardiomyocytes can lead to severe cardiac fibrosis and inflammation, as well as endothelial-to-mesenchymal transition and left ventricular dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Wuan-Geok Saw, Chen Yen Leow, Amaravadhi Harikishore, Joon Shin, Malcolm S. Cole, Wassihun Wedajo Aragaw, Priya Ragunathan, Pooja Hegde, Courtney C. Aldrich, Thomas Dick, Gerhard Gruber
Summary: This study conducted the first structure-function studies on PanD encoded by the nontuberculous mycobacterial lung pathogen Mycobacterium abscessus (Mab), revealing the differences and similarities of Mab and Mtb PanD. Additionally, a library of recombinant Mab PanD mutants based on structural information and PZA/POA resistant PanD mutations in Mtb identified a potent inhibitor of Mab PanD. The inhibitor showed electrostatic- and hydrogen bonding interaction with the target enzyme and exhibited antibacterial activity against the three subspecies of Mab.
ACS INFECTIOUS DISEASES
(2022)