Article
Chemistry, Medicinal
Paola Rota, Paolo La Rocca, Francesco Bonfante, Matteo Pagliari, Federica Cirillo, Marco Piccoli, Andrea Ghiroldi, Valentina Franco, Carlo Pappone, Pietro Allevi, Luigi Anastasia
Summary: This study focuses on the potential of C5- and C4-modified 2,3-unsaturated sialic acid (DANA) inhibitors and highlights their interaction with the hPIV1-HN enzyme. It shows that replacing the C5 isopropyl group in BCX 2798 with a trifluoroacetyl function increases inhibitory potency. The study also explores the special properties of the catalytic site of hPIV1-HN and presents a newly identified potent inhibitor with preferred C5 trifluoro-acetamido and C4 trifluoro-sulfonyl-amide groups.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Immunology
Fu-Lu Chu, Hong-Ling Wen, Gui-Hua Hou, Bin Lin, Wen-Qiang Zhang, Yan-Yan Song, Guijie Ren, Cheng-Xi Sun, Zhen-Mei Li, Zhiyu Wang
Summary: This study reveals that the mutated amino acids investigated play a critical role in the fusion process between the virus and cells, significantly reducing the virus' hemadsorption and fusogenic activities.
MICROBIAL PATHOGENESIS
(2021)
Article
Chemistry, Medicinal
Paola Rota, Francesco Bonfante, Luigi Anastasia, Paolo La Rocca, Matteo Pagliari, Marco Piccoli, Federica Cirillo, Andrea Ghiroldi, Valentina Franco, Carlo Pappone, Pietro Allevi
Summary: Global infections with Paramyxoviridae viruses, such as NDV and hPIVs, are a serious threat to animal and human health. The development of an efficient experimental NDV host model (chicken) may help evaluate the efficacy of hPIVs-HN inhibitors. Newly synthesized sialic acid derivatives showed high neuraminidase inhibitory activity against NDV, with four molecules confirming their in vitro inhibitory activity and low toxicity.
ACS INFECTIOUS DISEASES
(2023)
Article
Chemistry, Multidisciplinary
Asuka Shirakawa, Yoshiyuki Manabe, Roberta Marchetti, Kumpei Yano, Seiji Masui, Alba Silipo, Antonio Molinaro, Koichi Fukase
Summary: The fully sialylated tetraantennary N-glycan was synthesized for the first time using a specific strategy, and the synthesized compounds were used to study the recognition mechanism of neuraminidase.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Victor K. Outlaw, Ross W. Cheloha, Eric M. Jurgens, Francesca T. Bovier, Yun Zhu, Dale F. Kreitler, Olivia Harder, Stefan Niewiesk, Matteo Porotto, Samuel H. Gellman, Anne Moscona
Summary: Lower respiratory tract infections in children globally are largely caused by parainfluenza viruses (HPIVs), with no available vaccines or effective treatments against these pathogens. Research has shown that lipopeptides derived from HPIV3 F can inhibit infection, and the modification of the peptide backbone with beta-amino acid residues has resulted in improved antiviral activity and in vivo stability.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Physics, Fluids & Plasmas
Pedro A. Soria Ruiz, Falko Ziebert, Igor M. Kulic
Summary: This study investigates the physics of viral self-rolling states and reveals the mechanism of their motion, validating previous theories. The results indicate that viral rolling in the presence of enzymatic activity is statistically inevitable.
Article
Biochemistry & Molecular Biology
Sphamandla E. Mtambo, Samuel C. Ugbaja, Aganze G. Mushebenge, Bahijjahtu H. Abubakar, Mthobisi L. Ntuli, Hezekiel M. Kumalo
Summary: This study investigates the mechanism and dynamics of the E119V mutation on the peramivir-neuraminidase complex of the H7N9 virus. Molecular dynamic simulations and analysis reveal that the E119V substitution confers greater stability on the protein complex. This research provides valuable insights for future drug design and control of avian influenza.
Review
Biochemistry & Molecular Biology
Wenjuan Du, Erik de Vries, Frank J. M. van Kuppeveld, Mikhail Matrosovich, Cornelis A. M. de Haan
Summary: Human influenza A viruses originate from animal viruses, with HA and NA playing important roles in the virus particles, although the role of NA in host adaptation is less understood. NA plays a crucial role in adjusting the HA-NA balance of virus particles and affecting virus replication, likely influencing the viral host range.
Article
Medicine, Research & Experimental
Alexander L. Greninger, Ksenia Rybkina, Michelle J. Lin, Jennifer Drew-Bear, Tara C. Marcink, Ryan C. Shean, Negar Makhsous, Michael Boeckh, Olivia Harder, Francesca Bovier, Shana R. Burstein, Stefan Niewiesk, Bert K. Rima, Matteo Porotto, Anne Moscona
Summary: Respiratory viruses have the ability to evolve within the respiratory tract under the selective pressure of the host environment or drug treatment. Long-term infections in immunocompromised hosts lead to viral evolution and development of infectious variants. In chronic human parainfluenza virus 3 (HPIV3) infection, mutations favoring viral entry and persistence were observed, suggesting potential evolution of viruses to alter their biophysical characteristics to persist in the face of host-directed therapeutics.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Microbiology
Nan Shao, Bo Liu, Yan Xiao, Xinming Wang, Lili Ren, Jie Dong, Lilian Sun, Yafang Zhu, Ting Zhang, Fan Yang
Summary: This study investigated the genetic diversity and evolution of human parainfluenza viruses circulating in China by sequencing samples from patients infected with HPIV1-4 from 2012 to 2018. The results showed co-circulation of HPIV1-4 in China, with sub-clusters of HPIV3 also co-circulating. Recombination events were identified in the HN gene of HPIV3, and several amino acid substitution sites were found in the obtained sequences. These findings have implications for virus evolution, vaccine development, and monitoring respiratory diseases related to HPIVs.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Organic
Qingjiang Li, Jiatong Guo, Zhongwu Guo
Summary: A new and efficient method has been developed for the synthesis of C3-substituted sialyl glycals, allowing for the direct introduction of various functional groups. This method has demonstrated wide application scope by efficiently synthesizing a series of C3-aryl, alkyl, alkenyl, and alkynyl derivatives of sialyl glycal.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Virology
Mohammad Khavani, Aliyeh Mehranfar, Mohammad R. K. Mofrad
Summary: The mumps virus causes serious health issues, and designing an inhibitor for this virus is crucial. Using molecular dynamics simulations and quantum chemistry calculations, we investigated the affinity of different sialic acid-based compounds to the mumps virus HN protein. Our results show that the ligands form stable complexes with the HN protein through electrostatic, van der Waals, and hydrogen bond interactions, with electrostatic interactions playing a more significant role.
Article
Multidisciplinary Sciences
Julia Tabatabai, Paul Schnitzler, Christiane Prifert, Martin Schiller, Benedikt Weissbrich, Marie von Lilienfeld-Toal, Daniel Teschner, Karin Jordan, Carsten Mueller-Tidow, Gerlinde Egerer, Nicola Giesen
Summary: This study assessed the morbidity and mortality of parainfluenza virus (PIV) infections in immunocompromised patients by analyzing PIV infections in a hematology and stem cell transplantation (SCT) unit over three years. The results showed significant morbidity and mortality of PIV infection in these patients, with the possibility of long-term viral shedding and nosocomial transmission.
Article
Multidisciplinary Sciences
Chika Kikuchi, Aristotelis Antonopoulos, Shengyang Wang, Tadashi Maemura, Rositsa Karamanska, Chiara Lee, Andrew J. Thompson, Anne Dell, Yoshihiro Kawaoka, Stuart M. Haslam, James C. Paulson
Summary: The evolution of human H3N2 influenza viruses has led to a limited specificity of the hemagglutinin to a subset of glycan receptors, presenting challenges for virus recognition and vaccine production. By studying glyco-engineered cell lines, the authors demonstrate the importance of extended glycan receptors for the growth of recent H3N2 viruses and their relevance to vaccine production.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Organic
Pieter de Saint Aulaire, Jorin Hoogenboom, Michiel T. Uiterweerd, Han Zuilhof, Tom Wennekes
Summary: In this study, the synthesis of a carbocyclic sialic acid suitable for activity-based probes (ABPs) was attempted. Although the final conversion into an N-acetylneuraminic acid ABP was not achieved, this work presents a versatile route to potential future carbocyclic sialic acid derivatives.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Surekha Nimma, Weixi Gu, Mohammad K. Manik, Thomas Ve, Jeffrey D. Nanson, Bostjan Kobe
Summary: The TIR domains of IL-1R10 and IL-1R9 lack NADase activity, and their crystal structures provide insights into their functions.
Article
Chemistry, Medicinal
Yun Shi, Ibrahim M. El-Deeb, Veronika Masic, Lauren Hartley-Tassell, Andrea Maggioni, Mark von Itzstein, Thomas Ve
Summary: Fibrillarin is a crucial enzyme involved in the methylation of ribosomal RNAs, playing key roles in viral infections and cancer development. Understanding the structure of hFBL can lead to the design of novel drugs with selective inhibitory effects against it.
Article
Immunology
Zachary N. Phillips, Preeti Garai, Greg Tram, Gael Martin, Annelies Van den Bergh, Asma-Ul Husna, Megan Staples, Keith Grimwood, Amy Jennison, Patrice Guillon, Mark von Itzstein, Michael P. Jennings, Kenneth L. Brockman, John M. Atack
Summary: Lay is an autotransporter protein found in pathogenic Haemophilus and Neisseria species. Its expression status is reversible and related to pathogenicity in non-typeable Haemophilus influenzae. Understanding the role of Lay can provide insights into different pathological processes.
INFECTION AND IMMUNITY
(2022)
Article
Biochemistry & Molecular Biology
Saleh Alquethamy, Katherine Ganio, Zhenyao Luo, Sheikh I. Hossain, Andrew J. Hayes, Thomas Ve, Mark R. Davies, Evelyne Deplazes, Bostjan Kobe, Christopher A. McDevitt
Summary: In this study, A. baumannii ZnuA, a zinc-recruiting protein, was characterized using genomic, biochemical, and structural approaches. The findings revealed the high conservation of ZnuA and provided insight into the mechanism of zinc recruitment by ZnuA, expanding our understanding of the functional diversity of zinc-recruiting proteins.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2022)
Article
Microbiology
Zachary N. Phillips, Claudia Trappetti, Annelies Van Den Bergh, Gael Martin, Ainslie Calcutt, Victoria Ozberk, Patrice Guillon, Manisha Pandey, Mark von Itzstein, W. Edward Swords, James C. Paton, Michael P. Jennings, John M. Atack
Summary: S. pneumoniae, the world's foremost bacterial pathogen, encodes a phasevarion that results in differential expression of multiple genes. This study reveals that the phasevarion generates phenotypic differences relevant to pathobiology and that expression of conserved protein antigens varies with phasevarion switching. These findings are important for the selection of optimal candidates for inclusion in a rationally designed universal pneumococcal vaccine.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Annelies Van den Bergh, Patrice Guillon, Mark von Itzstein, Benjamin Bailly, Larissa Dirr
Summary: This study developed an in vitro medium-throughput screening assay to identify novel anti-HMPV drug candidates. Out of 2,400 compounds, 11 candidates were identified with inhibitory activity against HMPV infection. The mode of action of five candidates with low cytotoxicity was further described. Among them, the mycophenolic acid series displayed the highest levels of inhibition. It has significant potential for drug repurposing.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Annelies Van Den Bergh, Benjamin Bailly, Patrice Guillon, Mark von Itzstein, Larissa Dirr
Summary: Human metapneumoviruses (HMPV) have emerged as an important global pathogen, causing severe respiratory infections in young children, the elderly, and immunocompromised individuals. Despite the lack of available vaccines and drugs, the fusion protein of HMPV is considered a promising target for antiviral treatment.
ANTIVIRAL RESEARCH
(2022)
Review
Plant Sciences
Natsumi Maruta, Mitchell Sorbello, Bryan Y. J. Lim, Helen Y. McGuinness, Yun Shi, Thomas Ve, Bostjan Kobe
Summary: TIR domains are widely present in archaea, bacteria, and eukaryotes, often associated with immune functions. In plants, they are found in several proteins, including NLRs, NLR-like proteins, and TIR-only proteins. They are also found in effector proteins from phytopathogenic bacteria that suppress host immunity. TIR domains in plants and bacteria act as enzymes, cleaving NAD+ and other nucleotides. In dicot plants, TIR-derived signaling molecules activate downstream immune signaling proteins, EDS1 family proteins, and helper NLRs. Recent research has provided significant insights into the mechanism and signaling pathway of TIR domains.
CURRENT OPINION IN PLANT BIOLOGY
(2023)
Article
Virology
Gargi Kher, Charles Sabin, Jennifer H. Lun, Jessica M. Devant, Kerstin Ruoff, Anna D. Koromyslova, Mark von Itzstein, Marie Pancera, Grant S. Hansman
Summary: Human noroviruses are highly contagious and pose a major problem in closed institutions. New nanobodies have been developed that can efficiently block the HBGA binding site of the virus, providing valuable insights for the prevention of norovirus infections.
JOURNAL OF VIROLOGY
(2023)
Review
Clinical Neurology
Helen Y. McGuinness, Weixi Gu, Yun Shi, Bostjan Kobe, Thomas Ve
Summary: Axon degeneration is an early feature of many neurodegenerative disorders and is regulated by the NAD(+) metabolome. The pro-neurodegenerative NADase SARM1 triggers axon destruction, making it a potential therapeutic target. This review summarizes recent advances in understanding the molecular players involved in the SARM1-dependent axon degeneration program, as well as how SARM1 is regulated and activated in injured or diseased neurons.
Article
Multidisciplinary Sciences
Adam M. Bayless, Sisi Chen, Sam C. Ogden, Xiaoyan Xu, John D. Sidda, Mohammad K. Manik, Sulin Li, Bostjan Kobe, Thomas Ve, Lijiang Song, Murray Grant, Li Wan, Marc T. Nishimura
Summary: TIR domain proteins play important roles in cell death and immunity. Both plants and bacteria use TIR domains to produce cADPR isomers as potential immune signaling molecules. This study demonstrates the conservation and functional overlap of cADPR isomers produced by plant and prokaryotic TIRs, and clarifies the activation mechanism of the Thoeris system by plant TIRs. The findings highlight the distinct signaling requirements and diversity of small-molecule products generated by TIRs across kingdoms.
Article
Microbiology
Joanna E. Musik, Jessica Poole, Christopher J. Day, Thomas Haselhorst, Freda E. -C. Jen, Thomas Ve, Veronika Masic, Michael P. Jennings, Yaramah M. Zalucki
Summary: This study designed 11 peptides to mimic signal peptides that are inefficiently cleaved by LepB. The binding affinity and inhibitory potential of these peptides against LepB were assessed. It was found that the tryptophan residue in the signal peptide inhibited the cleavage of the peptide by LepB, and replacing this residue with alanine improved the cleavage efficiency.
MICROBIOLOGY SPECTRUM
(2023)
Review
Microbiology
Sulin Li, Mohammad K. Manik, Yun Shi, Bostjan Kobe, Thomas Ve
Summary: The Toll/interleukin-1 receptor (TIR) domain is found in various immune systems and has been studied extensively. Initially believed to be a protein-protein interaction module, recent research has shown that TIR domains can function as enzymes producing diverse nucleotide products. This knowledge has led to important advances in understanding the roles of TIR domain enzymes in bacterial and plant immune systems.
CURRENT OPINION IN MICROBIOLOGY
(2023)
Article
Chemistry, Inorganic & Nuclear
Anil K. Gorle, Alpeshkumar K. Malde, Chih-Wei Chang, Premraj Rajaratnam, Mark von Itzstein, Susan J. Berners-Price, Nicholas P. Farrell
Summary: [H-1, N-15] HSQC 2D NMR spectroscopy was used to study the aquation and subsequent coordinate covalent binding of the trinuclear clinical agent triplatin with two disaccharides, GlcNS(6S)-GlcA and GlcNS(6S)-IdoA(2S). The rate constant for sulfate displacement of the aqua ligand is higher than that for carboxylate displacement. Molecular dynamics calculations suggest that extra hydrogen-bonding interactions with the more sulfated disaccharide may prevent or diminish sulfate binding of the triplatin moiety.
INORGANIC CHEMISTRY
(2023)