Article
Multidisciplinary Sciences
Guha Asthagiri Arunkumar, Disha Bhavsar, Tiehai Li, Shirin Strohmeier, Veronika Chromikova, Fatima Amanat, Mehman Bunyatov, Patrick C. Wilson, Ali H. Ellebedy, Geert-Jan Boons, Viviana Simon, Robert P. de Vries, Florian Krammer
Summary: The recently discovered Wuhan spiny eel influenza virus (WSEIV) is more closely related to influenza B viruses than influenza A viruses, indicating a potentially new type of influenza virus; The NA-like protein of WSEIV has sialidase activity, while the HA-like protein binds specific sialic acid; Additionally, the HA and NA of WSEIV show limited antigenic conservation compared to influenza B virus, B/Malaysia/2506/2004.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Jens Dorna, Andreas Kaufmann, Viktoria Bockmann, Hartmann Raifer, Johanna West, Mikhail Matrosovich, Stefan Bauer
Summary: The study shows that IAVs with avian-like receptor specificity are less susceptible to infection by monocytes and lymphocyte subpopulations compared to human-like IAVs, while plasmacytoid dendritic cells and myeloid dendritic cells are equally susceptible to both types of IAVs. This tropism is correlated with the surface expression of different sialic acids. Despite reduced infectivity for PBMCs, avian-like IAVs are not less efficient in terms of cell activation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Alexey V. Danilenko, Natalia P. Kolosova, Alexander N. Shvalov, Tatyana N. Ilyicheva, Svetlana V. Svyatchenko, Alexander G. Durymanov, Julia A. Bulanovich, Natalia I. Goncharova, Ivan M. Susloparov, Vasiliy Y. Marchenko, Tatyana V. Tregubchak, Elena V. Gavrilova, Rinat A. Maksyutov, Alexander B. Ryzhikov
Summary: The study found mutations in major and minor variants in 57% of fatal cases in the 2018-2019 flu epidemic season in Russia, with a co-occurrence rate of 41% for D222G and D222N mutations. The high prevalence of HA D222G/N mutations in A(H1N1)pdm09 viruses and their association with fatal outcomes emphasize the importance of monitoring these mutations for assessing their epidemiological significance and considering disease prevention and treatment strategies.
Article
Chemistry, Multidisciplinary
Taryn M. Lucas, Chitrak Gupta, Meghan O. Altman, Emi Sanchez, Matthew R. Naticchia, Pascal Gagneux, Abhishek Singharoy, Kamil Godula
Summary: The study found that host glycan presentation and density can impact IAV virus recognition of specific receptors. Binding of H1N1 and H3N2 to alpha 2,3- and alpha 2,6-sialyllactose receptor arrays revealed different sensitivities to receptor presentation.
Article
Multidisciplinary Sciences
Micaela Trexler, Michelle Brusatori, Gregory Auner
Summary: Influenza virus mutates rapidly and traditional tools are not suitable for rapidly mutating pathogens like Influenza virus. Developing a novel capture coating using sialic acid as a binding receptor may provide a potential platform for future diagnostic and interrogation of viable Influenza virus.
Review
Biochemistry & Molecular Biology
Kevin Ciminski, Geoffrey P. Chase, Martin Beer, Martin Schwemmle
Summary: Emergent IAV strains from animal hosts typically have poor adaptation to humans and cannot establish sustained transmission. Despite frequent exposure to endemic IAV in animal populations, the number of pandemics in humans remains surprisingly low.
TRENDS IN MOLECULAR MEDICINE
(2021)
Article
Virology
Alexandra Duev-Cohen, Batya Isaacson, Orit Berhani, Yoav Charpak-Amikam, Nehemya Friedman, Yaron Drori, Michal Mandelboim, Ofer Mandelboim
Summary: The study found that NKp46 can recognize influenza B viruses, but the interaction strength is weaker compared to influenza A, and NKp46 is not crucial for eliminating influenza B.
Article
Chemistry, Medicinal
Marlena N. Stadtmueller, Sumati Bhatia, Pallavi Kiran, Malte Hilsch, Valentin Reiter-Scherer, Lutz Adam, Badri Parshad, Matthias Budt, Simon Klenk, Katrin Sellrie, Daniel Lauster, Peter H. Seeberger, Christian P. R. Hackenberger, Andreas Herrmann, Rainer Haag, Thorsten Wolff
Summary: The development of multi-valent sialic acid-based inhibitors for a variety of influenza A virus strains has been limited by the high genetic and structural variability of the targeted viral hemagglutinin (HA). By using sialylated polyglycerols and studying resistant mutants, a rationally designed inhibitor covering an extended spectrum of inhibited IAV strains was successfully created, highlighting the importance of integrating virological data with chemical synthesis and structural data for the development of sialylated polyglycerols towards broad anti-influenza compounds.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ananyaa Agrawal, Pratibha Chanana, Vikas Yadav, Vilakshan Bhutani, Naidu Subbarao, Aradhana Srivastava
Summary: The objective of this study was to identify potential inhibitors of Influenza surface HA. FMNNa and FMNCa were found to exhibit potential as HA inhibitors through in silico studies and MD simulations.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Infectious Diseases
Jiqing Li, Guohua Deng, Jianzhong Shi, Yaping Zhang, Xianying Zeng, Guobin Tian, Yongping Jiang, Liling Liu, Huihui Kong, Hualan Chen
Summary: H3N2 avian influenza viruses in poultry farms in China have complex gene constellations derived from different sources, but none have become dominant. Although these viruses have avian-type receptor-binding preference, most of them can replicate without preadaptation and cause weight loss in mice. This study highlights the potential threat of H3N2 AIVs to public health and emphasizes the need for continued surveillance in live poultry markets and poultry farms.
TRANSBOUNDARY AND EMERGING DISEASES
(2023)
Article
Cell Biology
Ruipeng Lei, Andrea Hernandez Garcia, Timothy J. C. Tan, Qi Wen Teo, Yiquan Wang, Xiwen Zhang, Shitong Luo, Satish K. Nair, Jian Peng, Nicholas C. Wu
Summary: Influenza neuraminidase (NA) has different levels of tolerance to mutations, with antigenic regions showing high mutational tolerance and solvent-exposed regions showing low mutational tolerance. Protein stability is an important factor affecting the fitness of NA mutations. The study's findings on NA's evolutionary potential and biophysical constraints provide insights for NA-based vaccine design.
Article
Chemistry, Analytical
Ji Hong Kim, Chae Hwan Cho, Jae Hwan Shin, Moon Seop Hyun, Eunha Hwang, Tae Jung Park, Jong Pil Park
Summary: An electrochemical biosensor was developed to detect the HA protein in the envelope of the influenza virus, using high-affinity peptide-displaying phage particles identified through phage display technology. The sensor showed good performance characteristics, including low limit of detection, high reproducibility, and compatibility with human plasma samples. The sensor system demonstrated advantages such as low cost, rapid analysis, and minimal sample volume requirement, making it suitable for rapid and effective detection of the influenza virus antigen.
SENSORS AND ACTUATORS B-CHEMICAL
(2021)
Article
Chemistry, Medicinal
Goran Bajic, Stephen C. Harrison
Summary: The study describes cross-reactive human antibodies recognizing influenza B viruses that have undergone nearly 80 years of antigenic drift. The structures of the antibodies show strong similarities to their influenza A counterparts in engaging the receptor-binding site of the viral hemagglutinin, despite structural differences between influenza A and B. These antibodies readily cross-react with both influenza B Victoria and Yamagata lineages, and are all encoded by IGHV3-9/IGK1-33. Further research will provide insights into the prevalence of these antibodies in the human population.
ACS INFECTIOUS DISEASES
(2021)
Letter
Immunology
Wenming Jiang, Chunxia Dong, Shuo Liu, Cheng Peng, Xin Yin, Shaobo Liang, Lin Zhang, Jinping Li, Xiaohui Yu, Yang Li, Jingjing Wang, Guangyu Hou, Zheng Zeng, Hualei Liu
Summary: A novel highly pathogenic avian influenza A(H5N6) clade 2.3.4.4b virus was isolated from a poultry market in China that a person with a confirmed case had visited. Most genes of the avian and human H5N6 isolates were closely related. The virus also exhibited distinct antigenicity to the Re-11 vaccine strain.
EMERGING INFECTIOUS DISEASES
(2022)
Article
Multidisciplinary Sciences
Wayne D. Harshbarger, Derrick Deming, Gordon J. Lockbaum, Nattapol Attatippaholkun, Maliwan Kamkaew, Shurong Hou, Mohan Somasundaran, Jennifer P. Wang, Robert W. Finberg, Quan Karen Zhu, Celia A. Schiffer, Wayne A. Marasco
Summary: This study presents structural details of the human antibody 3I14 recognizing HA from various influenza A viruses, highlighting the binding mechanism and potential implications for universal vaccine design.
NATURE COMMUNICATIONS
(2021)
Article
Infectious Diseases
Sue C. Nang, Mengyao Li, Marina Harper, Eric Mandela, Phillip J. Bergen, Jean-Marc Rolain, Yan Zhu, Tony Velkov, Jian Li
Summary: This study investigated the concentration-dependent transcriptomic responses of mcr-harbouring E. coli to polymyxin treatment. The results revealed that cell envelope remodelling, pEtN modification, iron acquisition, and oxidative stress protective mechanisms play a key role in the survival of mcr-carrying E. coli treated with polymyxin.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Article
Microbiology
Zhi Ying Kho, Mohammad A. K. Azad, Mei-Ling Han, Yan Zhu, Cheng Huang, Ralf B. Schittenhelm, Thomas Naderer, Tony Velkov, Joel Selkrig, Qi (Tony) Zhou, Jian Li
Summary: This study examines the impact of host-pathogen-antibiotic interaction on the opportunistic pathogen Acinetobacter baumannii. The findings reveal that macrophages and polymyxins work together to disrupt the bacteria's stress tolerance strategies, affecting its survival in host cells. The discovery of potential druggable targets and the mechanistic understanding of this interaction contribute to the optimization of antibiotic use and the development of new antimicrobial strategies against multidrug-resistant bacterial infections.
Article
Multidisciplinary Sciences
Sara Oberrauch, Jing Lu, Linda Cornthwaite-Duncan, Maytham Hussein, Jian Li, Gauri Rao, Tony Velkov
Summary: This article introduces a unique method of treating brain infections through intraventricular delivery of antibiotics. Researchers have developed a simple surgical procedure to implant a guide cannula reaching into the lateral ventricle, allowing for drug injection and flow control.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Chemistry, Multidisciplinary
Nitin A. Patil, Varsha J. Thombare, Rong Li, Xiaoji He, Jing Lu, Heidi H. Yu, Hasini Wickremasinghe, Kavya Pamulapati, Mohammad A. K. Azad, Tony Velkov, Kade D. Roberts, Jian Li
Summary: Peptide-Peptide Nucleic Acid (PNA) conjugates have shown potential in developing novel antisense antimicrobials. The efficiency of Cys-CINA conjugation was investigated for synthesizing peptide-PNA conjugates, which demonstrated improved antimicrobial activity against multidrug-resistant Gram-negative bacteria.
FRONTIERS IN CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Maytham Hussein, Rafah Allobawi, Irini Levou, Mark A. T. Blaskovich, Gauri G. Rao, Jian Li, Tony Velkov
Summary: Polymyxins combined with synthetic cannabidiol showed synergistic antibacterial activity against both polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii isolates. Metabolomics study revealed that the combination therapy significantly perturbed metabolic pathways involved in bacterial cell envelope and membrane lipids. The study suggests the possibility of cannabidiol repositioning, in combination with polymyxins, for treatment of multidrug-resistant Gram-negative infections.
Article
Biochemistry & Molecular Biology
Chongshan Dai, Jiahao Lin, Hui Li, Zhangqi Shen, Yang Wang, Tony Velkov, Jianzhong Shen
Summary: Curcumin, an important component of turmeric, is considered a safe oral treatment for bacterial infections and has exhibited antibacterial activities against both Gram-negative and Gram-positive bacteria. Its antibacterial actions include disrupting bacterial membranes, inhibiting the production of bacterial virulence factors and biofilm formation, as well as inducing oxidative stress. Additionally, curcumin acts as a broad-spectrum antibacterial adjuvant, showing marked additive or synergistic effects with conventional antibiotics or non-antibiotic compounds.
Article
Infectious Diseases
Mengyao Li, Mohammad A. K. Azad, Maizbha U. Ahmed, Yan Zhu, Jiangning Song, Fanfan Zhou, Hak-Kim Chan, Tony Velkov, Qi Tony Zhou, Jian Li
Summary: This study elucidated the complex interplay of multiple signalling networks in cellular responses to polymyxin-induced toxicity using a human lung epithelial cell model. The findings revealed that polymyxin affects cell cycle, DNA repair, and DNA replication pathways, while inhibiting the NF-kappa B and NOD-like receptor signalling pathways. Additionally, several hub genes, including PLK1, CDK20, CCNA2, BUB1, and BUB1B, were found to be affected by polymyxin treatment. Cell cycle, DNA damage, and pro-inflammatory signalling pathways play key roles in polymyxin-induced toxicity in human lung epithelial cells.
Article
Chemistry, Medicinal
Xukai Jiang, Meiling Han, Kevin Tran, Nitin A. Patil, Wendong Ma, Kade D. Roberts, Min Xiao, Bjorn Sommer, Falk Schreiber, Lushan Wang, Tony Velkov, Jian Li
Summary: Multidrug-resistant Gram-negative bacteria pose a serious threat to modern medicine. Current structural biology methods are unable to resolve the structure of bacterial outer membranes, which limits our understanding of antibiotic penetration through the membrane and the discovery of new antibiotics. In this study, we developed biologically relevant models of outer membranes and used molecular dynamics simulations to investigate the resistance mechanisms of Pseudomonas aeruginosa to polymyxins. Our computational strategy, validated by experimental assays, shows promise in accelerating the discovery of lipopeptides against bacterial superbugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Food Science & Technology
Chongshan Dai, Subhajit Das Gupta, Zhanhui Wang, Haiyang Jiang, Tony Velkov, Jianzhong Shen
Summary: In this review, the authors summarized the current knowledge and challenges related to T-2 toxin-induced cardiotoxicity, and discussed potential treatment approaches. The cardiotoxicity caused by T-2 toxin involves various cellular pathways and mechanisms, including oxidative stress, mitochondrial dysfunction, and inflammatory responses. Antioxidant supplementation, induction of autophagy, and blockade of inflammatory signaling may provide protective effects against T-2 toxin-induced cardiac toxicity.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Multidisciplinary Sciences
Rajnikant Sharma, Shekhar Yeshwante, Quentin Valle, Maytham Hussein, Varsha Thombare, Sean Michael McCann, Robert Maile, Jian Li, Tony Velkov, Gauri Rao
Summary: This article presents a simple and reproducible rat burn model that mimics clinical situations and induces immune dysregulation and bacterial infections. This model is of considerable utility for the development of new topical antibiotic drugs for burn wound and infections.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Review
Microbiology
Augustine Koh Jing Jie, Maytham Hussein, Gauri G. G. Rao, Jian Li, Tony Velkov
Summary: Multidrug-resistant Gram-negative pathogens are a significant public health threat, with limited options for treatment due to the lack of new antibiotics and increasing resistance. Combining conventional antibiotics with non-antibiotics has emerged as a promising strategy for combating these pathogens.
Article
Biochemistry & Molecular Biology
Ilona Turek, Trang H. Nguyen, Charles Galea, Isaiah Abad, Lubna Freihat, David T. Manallack, Tony Velkov, Helen Irving
Summary: Interleukin-1 receptor-associated kinase 3 (IRAK3) regulates cellular responses to IL-1Rs and TLRs, leading to decreased pro-inflammatory cytokines and suppressed inflammation. The mechanism of IRAK3's action is unknown, but it functions as a guanylate cyclase and its cGMP product inhibits NF-κB activity. By mutagenesis and analysis, we identified residues in and near the catalytic center of IRAK3 that affect NF-κB activity and subcellular localization in HEK293T cells. Mutant IRAK3 variants with reduced cGMP generation capacity and altered NF-κB activity fail to rescue IRAK3 function in LPS-stimulated THP-1 monocytes unless a cGMP analog is present.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Nitin A. Patil, Wendong Ma, Xukai Jiang, Xiaoji He, Heidi H. Yu, Hasini Wickremasinghe, Jiping Wang, Philip E. Thompson, Tony Velkov, Kade D. Roberts, Jian Li
Summary: Polymyxins, including polymyxin B and colistin, are used as a last resort to treat life-threatening multidrug-resistant Gram-negative bacterial infections. However, their clinical use is limited by toxicity and increasing resistance. This study explores the role of the conserved position 10 threonine residue in polymyxin's structure and reveals the requirements for antibacterial activity. These findings provide vital information for developing safer and more effective next-generation polymyxin antibiotics.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Infectious Diseases
Mengyao Li, Mohammad A. K. Azad, Philip E. Thompson, Kade D. Roberts, Tony Velkov, Yan Zhu, Jian Li
Summary: Polymyxins are last-line antibiotics used to treat Gram-negative 'superbugs'. However, they can cause nephrotoxicity in up to 60% of patients. This study investigated the transcriptomic responses of human renal tubular cells to polymyxins and identified potential targets for designing safer new-generation polymyxins.
Article
Biochemistry & Molecular Biology
Maytham Hussein, Labell J. M. Wong, Jinxin Zhao, Vanessa E. Rees, Rafah Allobawi, Rajnikant Sharma, Gauri G. Rao, Mark Baker, Jian Li, Tony Velkov
Summary: This study investigates the synergistic antibacterial activity of polymyxin B in combination with the antifungal caspofungin against Klebsiella pneumoniae, and analyzes the killing mechanisms of this combination.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
