Article
Biology
Lorena Zuzic, Jan K. Marzinek, Ganesh S. Anand, Jim Warwicker, Peter J. Bond
Summary: This study utilized large-scale molecular dynamics simulations to investigate six flaviviruses, leading to the discovery of shared hotspots and conserved cryptic sites. A cluster-dependent mechanism was proposed to explain the role of cluster protonation in regulating the formation of the fusogenic trimer in flaviviruses.
Article
Parasitology
Anton Spadar, Jody E. Phelan, Ernest Diez Benavente, Monica Campos, Lara Ferrero Gomez, Fady Mohareb, Taane G. Clark, Susana Campino
Summary: The study found that almost all flavivirus EVEs in the Ae. aegypti genome originate from four distinct viral integration events and are highly conserved across diverse geographical samples. In contrast, flavivirus EVEs in the Ae. albopictus genome may originate from up to nine integration events and show low levels of conservation, even within samples from narrow geographical ranges. This suggests different evolutionary origins and potential functional roles for EVEs of Ae. aegypti and Ae. albopictus, as they belong to different phylogenetic clades and display varying levels of conservation.
PARASITES & VECTORS
(2021)
Article
Multidisciplinary Sciences
Christine Toelzer, Kapil Gupta, Sathish K. N. Yadav, Lorna Hodgson, Maia Kavanagh Williamson, Dora Buzas, Ufuk Borucu, Kyle Powers, Richard Stenner, Kate Vasileiou, Frederic Garzoni, Daniel Fitzgerald, Christine Payre, Gunjan Gautam, Gerard Lambeau, Andrew D. Davidson, Paul Verkade, Martin Frank, Imre Berger, Christiane Schaffitzel
Summary: This study reveals the importance of fatty acid binding in pathogenic coronavirus infection and replication. The spike glycoprotein of SARS-CoV-2 and its variants bind to a fatty acid called linoleic acid, which stabilizes the locked conformation of the spike protein and interferes with virus infectivity. In contrast, a mutation in a common cold-causing coronavirus abolishes this binding. Treatment with linoleic acid inhibits viral replication and reduces the number of deformed virus particles. These findings suggest that targeting fatty acid binding could be a potential strategy for combating COVID-19.
Article
Immunology
Hong Zheng, Aditya M. Rao, Denis Dermadi, Jiaying Toh, Lara Murphy Jones, Michele Donato, Yiran Liu, Yapeng Su, Cheng L. Dai, Sergey A. Kornilov, Minas Karagiannis, Theodoros Marantos, Yehudit Hasin-Brumshtein, Yudong D. He, Evangelos J. Giamarellos-Bourboulis, James R. Heath, Purvesh Khatri
Summary: Viral infections trigger a distinct host response, with severe infections associated with increased hematopoiesis, myelopoiesis, and myeloid-derived suppressor cells. Protective and detrimental gene modules were identified to define different trajectories of outcomes, providing insights for the development of diagnostics and host-directed therapies to improve global pandemic preparedness.
Article
Virology
Iris Medits, Franz X. Heinz, Karin Stiasny
Summary: The conserved tryptophan in the major envelope protein E of flaviviruses, or another big hydrophobic amino acid in the same position, plays a crucial role in virus assembly and infectivity by contributing to the stability of infectious particles.
Article
Cell Biology
Shaojun Zhang, Wenze Huang, Lili Ren, Xiaohui Ju, Mingli Gong, Jian Rao, Lei Sun, Pan Li, Qiang Ding, Jianwei Wang, Qiangfeng Cliff Zhang
Summary: Comparative analysis revealed common and virus-specific host responses, identifying vRNA-associated proteins that either promote or restrict viral infection. The study highlighted how SARS-CoV-2 hijacks the host factor IGF2BP1 to stabilize vRNA and enhance viral translation. Interactome-informed drug repurposing led to the identification of potential broad-spectrum antivirals, including Cepharanthine and Trifluoperazine, with efficacy against the emerging SARS-CoV-2 B.1.351 variant.
Article
Biochemistry & Molecular Biology
Joe McKellar, Mary Arnaud-Arnould, Laurent Chaloin, Marine Tauziet, Charlotte Arpin-Andre, Oriane Pourcelot, Mickael Blaise, Olivier Moncorge, Caroline Goujon
Summary: The N-terminal domain of HsMX1 protein is essential for its antiviral activity against influenza A virus, Vesicular Stomatitis Virus, and La Crosse virus, as demonstrated by mutagenesis, imaging, and biochemical approaches. A highly conserved leucine within this region is crucial for the antiviral activity of human, mouse, and bat MX1 proteins. Mutation of this leucine does not affect GTPase activity or oligomerization capabilities, but alters MX1 protein subcellular localization.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Peter A. Ivanov, Tatiana V. Gasanova, Maria N. Repina, Andrey A. Zamyatnin Jr
Summary: Virus-specific proteins can trigger hypersensitive response (HR) in plants, which is a type of cell death. The main cell death signaling pathway involves the interaction between HR-inducing proteins and nucleotide-binding leucine-rich repeats (NLR) proteins encoded by plant resistance genes. NLR proteins can act as both sensors and helpers, or form an activation network leading to oligomerization and formation of membrane-associated resistosomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Virology
Gabriel Dupre, Claire Hoede, Thomas Figueroa, Pierre Bessiere, Stephane Bertagnoli, Mariette Ducatez, Christine Gaspin, Romain Volmer
Summary: The study investigated the RNA structure features of the sources of infection of highly pathogenic avian influenza viruses (HPAIVs) of H7 subtype, and found that most of the American lineage ancestors leading to H7 emergences via recombination shared the same viral RNA structure topology at the HA1/HA2 boundary region.
Review
Biochemistry & Molecular Biology
Joshua M. Hardy, Rhys A. Dunstan, Trevor Lithgow, Fasseli Coulibaly
Summary: Most phages inject their genomic material into their host through a tubular assembly known as a tail. The diversity of tailed phages can be classified into three archetypes: contractile tails, short non-contractile tails, and long and flexible non-contractile tails. Recent studies have revealed the structural features of Siphoviridae-like tail tubes and identified common and distinct characteristics.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Article
Virology
Joey McGregor, Joshua M. Hardy, Chan-Sien Lay, Irene Boo, Michael Piontek, Manfred Suckow, Fasseli Coulibaly, Pantelis Poumbourios, Rob J. Center, Heidi E. Drummer
Summary: There is currently no vaccine for hepatitis C virus, but researchers have developed a virus-like particle vaccine that can induce the production of neutralizing antibodies and has shown immunogenicity in guinea pigs. This vaccine platform holds promise as a low-cost candidate for large-scale production of an HCV vaccine.
JOURNAL OF VIROLOGY
(2022)
Article
Infectious Diseases
Nias Y. G. Peng, Alberto A. Amarilla, Leon E. Hugo, Naphak Modhiran, Julian D. J. Sng, Andrii Slonchak, Daniel Watterson, Yin Xiang Setoh, Alexander A. Khromykh
Summary: The NS5-M114V mutation has little impact on the replication and transmission potential of the Zika virus in cells and in vivo, but slightly prolongs viremia in mice and reduces mosquito infection and dissemination rates.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Chemistry, Multidisciplinary
Scott E. Guimond, Courtney J. Mycroft-West, Neha S. Gandhi, Julia A. Tree, Thuy T. Le, C. Mirella Spalluto, Maria Humbert, Karen R. Buttigieg, Naomi Coombes, Michael J. Elmore, Matthew Wand, Kristina Nystrom, Joanna Said, Yin Xiang Setoh, Alberto A. Amarilla, Naphak Modhiran, Julian D. J. Sng, Mohit Chhabra, Paul R. Young, Daniel J. Rawle, Marcelo A. Lima, Edwin A. Yates, Richard Karlsson, Rebecca L. Miller, Yen-Hsi Chen, Ieva Bagdonaite, Zhang Yang, James Stewart, Dung Nguyen, Stephen Laidlaw, Edward Hammond, Keith Dredge, Tom M. A. Wilkinson, Daniel Watterson, Alexander A. Khromykh, Andreas Suhrbier, Miles W. Carroll, Edward Trybala, Tomas Bergstrom, Vito Ferro, Mark A. Skidmore, Jeremy E. Turnbull
Summary: This study found that the synthetic HS mimetic pixatimod can interact with the receptor binding domain of the SARS-CoV-2 spike protein and directly inhibit its binding to ACE2. The results show that pixatimod can effectively inhibit the infection of multiple clinical isolates of SARS-CoV-2 virus and has broad potency against various variants. In a mouse model, pixatimod also reduces viral titers and weight loss. This study provides strong evidence for the potential use of synthetic HS mimetics as a therapeutic approach for COVID-19.
ACS CENTRAL SCIENCE
(2022)
Article
Immunology
Christopher L. D. McMillan, Armira Azuar, Jovin J. Y. Choo, Naphak Modhiran, Alberto A. Amarilla, Ariel Isaacs, Kate E. Honeyman, Stacey T. M. Cheung, Benjamin Liang, Maria J. Wurm, Paco Pino, Joeri Kint, Germain J. P. Fernando, Michael J. Landsberg, Alexander A. Khromykh, Jody Hobson-Peters, Daniel Watterson, Paul R. Young, David A. Muller
Summary: The study investigated a novel vaccination strategy using a modified HexaPro S protein subunit vaccine, which generated potent antibody responses capable of neutralizing various SARS-CoV-2 variants in mice. The results demonstrated the potential of this alternative vaccination approach to mitigate the impact of emerging viral variants.
Article
Multidisciplinary Sciences
Michaela D. J. Blyton, Paul R. Young, Ben D. Moore, Keith J. Chappell, Stephen Goff
Summary: The distribution and genetic characteristics of koala retrovirus differ between northern and southern populations. Southern koalas carry partial endogenous viral sequences, while northern koalas carry exogenous viral subtypes. This suggests that the evolution and transmission of the koala retrovirus are influenced by geographic factors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Eduardo A. Albornoz, Alberto A. Amarilla, Naphak Modhiran, Sandra Parker, Xaria X. Li, Danushka K. Wijesundara, Julio Aguado, Adriana Pliego Zamora, Christopher L. D. McMillan, Benjamin Liang, Nias Y. G. Peng, Julian D. J. Sng, Fatema Tuj Saima, Jenny N. Fung, John D. Lee, Devina Paramitha, Rhys Parry, Michael S. Avumegah, Ariel Isaacs, Martin W. Lo, Zaray Miranda-Chacon, Daniella Bradshaw, Constanza Salinas-Rebolledo, Niwanthi W. Rajapakse, Ernst J. Wolvetang, Trent P. Munro, Alejandro Rojas-Fernandez, Paul R. Young, Katryn J. Stacey, Alexander A. Khromykh, Keith J. Chappell, Daniel Watterson, Trent M. Woodruff
Summary: COVID-19 infection may lead to neurological symptoms similar to Parkinson's disease. The study found that SARS-CoV-2 and spike protein can directly activate the NLRP3 inflammasome in microglial cells, which may contribute to the development of neuroinflammation.
MOLECULAR PSYCHIATRY
(2023)
Article
Hematology
Jody Hobson-Peters, Alberto A. Amarilla, Lina Rustanti, Denese C. Marks, Eileen Roulis, Alexander A. Khromykh, Naphak Modhiran, Daniel Watterson, Stefan Reichenberg, Frank Tolksdorf, Chryslain Sumian, Axel Seltsam, Ute Gravemann, Helen M. Faddy
Summary: The THERAFLEX MB-Plasma and THERAFLEX UV-Platelets systems were found to effectively reduce the infectivity of SARS-CoV-2 in plasma and platelets, respectively.
Letter
Virology
Peter Speck, Jason Mackenzie, Rowena A. Bull, Barry Slobedman, Heidi Drummer, Johanna Fraser, Lara Herrero, Karla Helbig, Sarah Londrigan, Gregory Moseley, Natalie Prow, Grant Hansman, Robert Edwards, Chantelle Ahlenstiel, Allison Abendroth, David Tscharke, Jody Hobson-Peters, Robson Kriiger-Loterio, Rhys Parry, Glenn Marsh, Emma Harding, David A. Jacques, Matthew J. Gartner, Wen Shi Lee, Julie McAuley, Paola Vaz, Frank Sainsbury, Michelle D. Tate, Jane Sinclair, Allison Imrie, Stephen Rawlinson, Andrew Harman, Jillian M. Carr, Ebony A. Monson, Merilyn Hibma, Timothy J. Mahony, Thomas Tu, Robert J. Center, Lok Bahadur Shrestha, Robyn Hall, Morgyn Warner, Vernon Ward, Danielle E. Anderson, Nicholas S. Eyre, Natalie E. Netzler, Alison J. Peel, Peter Revill, Michael Beard, Alistair R. Legione, Alexandra J. Spencer, Adi Idris, Jade Forwood, Subir Sarker, Damian F. J. Purcell, Nathan Bartlett, Joshua M. Deerain, Bruce J. Brew, Sassan Asgari, Helen Farrell, Alexander Khromykh, Daniel Enosi Tuipulotu, David Anderson, Sevim Mese, Yaman Tayyar, Kathryn Edenborough, Jasim Muhammad Uddin, Abrar Hussain, Connor J. I. Daymond, Jacinta Agius, Karyn N. Johnson, Paniz Shirmast, Mahdi Abedinzadeshahri, Robin MacDiarmid, Caroline L. Ashley, Jay Laws, Lucy L. Furfaro, Thomas D. Burton, Stephen M. R. Johnson, Zahra Telikani, Mary Petrone, Justin A. Roby, Carolyn Samer, Andreas Suhrbier, April van der Kamp, Anthony Cunningham, Celeste Donato, Jackie Mahar, Wesley D. Black, Subhash Vasudevan, Roman Lenchine, Kirsten Spann, Daniel J. Rawle, Penny Rudd, Jessica Neil, Richard Kingston, Timothy P. Newsome, Ki Wook Kim, Johnson Mak, Kym Lowry, Nathan Bryant, Joanne Meers, Jason A. Roberts, Nigel McMillan, Larisa I. Labzin, Andrii Slonchak, Leon E. Hugo, Bennett Henzeler, Natalee D. Newton, Cassandra T. David, Patrick C. Reading, Camille Esneau, Tatiana Briody, Najla Nasr, Donna McNeale, Brian McSharry, Omid Fakhri, Bethany A. Horsburgh, Grant Logan, Paul Howley, Paul Young
JOURNAL OF VIROLOGY
(2023)
Article
Multidisciplinary Sciences
Michael J. Roy, Minglyanna G. Surudoi, Ashleigh Kropp, Jianmei Hou, Weiwen Dai, Joshua M. Hardy, Lung-Yu Liang, Thomas R. Cotton, Bernhard C. Lechtenberg, Toby A. Dite, Xiuquan Ma, Roger J. Daly, Onisha Patel, Isabelle S. Lucet
Summary: PEAK pseudokinases regulate cell migration, invasion and proliferation by recruiting key signaling proteins to the cytoskeleton. The researchers elucidate the molecular details of key PEAK signaling interactions with the adapter proteins CrkII and Grb2 and the scaffold protein 14-3-3. They identify a conserved high affinity 14-3-3 motif on PEAK3 and demonstrate its role as a molecular switch to regulate CrkII binding and signaling via Grb2.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Annalisa L. E. Carli, Joshua M. Hardy, Hanadi Hoblos, Matthias Ernst, Isabelle S. Lucet, Michael Buchert
Summary: This review examines the functions of DCLK1 and predicts the effects of somatic missense mutations on its functions. DCLK1 is a microtubule-associated protein that plays a role in cancer development. Mutations in DCLK1 primarily affect its binding and stability with microtubules, leading to altered microtubule dynamics.
Editorial Material
Virology
Adriana Pliego Zamora, Jaehyeon Kim, Parimala R. Vajjhala, Sara J. Thygesen, Daniel Watterson, Naphak Modhiran, Helle Bielefeldt-Ohmann, Katryn J. Stacey
Summary: Severe dengue virus infection can lead to gastrointestinal symptoms and tissue damage, potentially causing severe disease. Inflammation in dengue infection occurs earlier and is more severe in the gastrointestinal tract compared to other tissues. The breakdown of the gut barrier may exacerbate inflammation and promote the development of severe dengue.
JOURNAL OF VIROLOGY
(2023)
Article
Chemistry, Organic
Yizhou Liu, Benjamin Jian Wen Liang, Naphak Modhiran, G. Paul Savage, Daniel Watterson, Craig M. Williams
Summary: Pirfenidone, an oral medication used for idiopathic pulmonary fibrosis (IPF), is proposed to treat post-COVID pneumonia pulmonary fibrosis (PF). However, it has side effects. In this study, cubane and cyclooctatetraene (COT) derivatives of pirfenidone were prepared as potential replacements to explore activity changes. The COT derivative showed similar activity and cytotoxicity to pirfenidone in anti-virus and ACE2 inhibition assays.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Cell Biology
Julio Aguado, Alberto A. Amarilla, Atefeh Taherian Fard, Eduardo A. Albornoz, Alexander Tyshkovskiy, Marius Schwabenland, Harman K. Chaggar, Naphak Modhiran, Cecilia Gomez-Inclan, Ibrahim Javed, Alireza A. Baradar, Benjamin Liang, Lianli Peng, Malindrie Dharmaratne, Giovanni Pietrogrande, Pranesh Padmanabhan, Morgan E. Freney, Rhys Parry, Julian D. J. Sng, Ariel Isaacs, Alexander A. Khromykh, Guillermo Valenzuela Nieto, Alejandro Rojas-Fernandez, Thomas P. Davis, Marco Prinz, Bertram Bengsch, Vadim N. Gladyshev, Trent M. Woodruff, Jessica C. Mar, Daniel Watterson, Ernst J. Wolvetang
Summary: Senescent cells play a significant role in brain aging and COVID-19-induced neuropathology, and senolytic therapy shows therapeutic potential in protecting against COVID-19-induced brain aging.