Article
Biochemistry & Molecular Biology
Joanna Pianka, Natalia Gruba, Adam Lesner
Summary: West Nile Virus (WNV), a member of the flavivirus group, can cause mild or severe forms of infection, with no known medications for prevention. The research aimed to develop specific tools to determine the activity of the WNV serine proteinase.
BIOORGANIC CHEMISTRY
(2023)
Article
Virology
Alanna C. Tseng, Vivek R. Nerurkar, Kabi R. Neupane, Helmut Kae, Pakieli H. Kaufusi
Summary: NS3 protein needs to cooperate with NS2B to be properly localized to the endoplasmic reticulum and exhibit enzymatic activity, and NS2B may also play an additional role in recruiting NS3. Targeting the interaction between NS2B and NS3 could be a potential avenue for antiviral drug discovery.
Review
Biochemistry & Molecular Biology
Saan Voss, Christoph Nitsche
Summary: West Nile virus infections can cause severe neurological symptoms, but there are currently no vaccines or specific antiviral therapies available. The viral protease NS2B-NS3 is considered a promising target, but protease inhibitors have not yet reached clinical trials. Substrate-derived peptidomimetics have aided in understanding the protease's active state, while new compounds aim to expand drug discovery efforts.
RSC MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Suhaina Supian, Machap Chandradevan, Muhamad Aizuddin Ahmad, Lina Rozano, Mohd Shukri Mat Ali, Sanimah Simoh
Summary: The inhibitory activity of Lepisanthes fruticosa pulp extract against NS2B-NS3 proteases from DENV2 and WNV suggests the potential of this fruit species for antiviral development. Metabolites from the groups of flavonols, flavones, and sterols in L. fruticosa pulp may contribute to its inhibitory properties.
PHARMACOGNOSY MAGAZINE
(2021)
Article
Multidisciplinary Sciences
Haley S. Caldwell, Lili Kuo, Janice D. Pata, Alan P. Dupuis Ii, Jamie J. Arnold, Calvin Yeager, Jessica Stout, Cheri A. Koetzner, Anne F. Payne, Sean M. Bialosuknia, Elyse M. Banker, Taylor A. Nolen, Craig E. Cameron, Alexander T. Ciota
Summary: The most common arbovirus in the United States, West Nile virus (WNV), is transmitted between Culex spp. mosquitoes and birds. A specific mutation, NS3 P319L, was found to affect the adaptation of the virus to vertebrate hosts and its transmissibility by mosquitoes. This study highlights the importance of intrahost sequence data in understanding host-specific adaptation mechanisms.
Article
Mathematics, Applied
Liqiong Pu, Zhigui Lin
Summary: This paper discusses a model of West Nile virus on a growing domain, considering habitat expansion of mosquitoes due to climate warming. The basic reproduction number related to the growing rate and diffusion rate is introduced, and conditions for virus elimination or spread are deduced. Results show that domain growth increases infection risk and hinders control efforts for WNv.
MATHEMATICAL METHODS IN THE APPLIED SCIENCES
(2021)
Article
Virology
Hegger Fritsch, Felicidade Mota Pereira, Erica Azevedo Costa, Vagner Fonseca, Stephane Tosta, Joilson Xavier, Flavia Levy, Carla de Oliveira, Gabriela Menezes, Jaqueline Lima, Lenisa Santos, Luciana Silva, Vanessa Nardy, Marcela Kelly Gomez Astete, Beatriz Senra Alvares da Silva Santos, Nagila Rocha Aguiar, Maria Isabel Maldonado Coelho Guedes, Guilherme Canhestro de Faria, Ronaldo Furtini, Safira Rachel Milanez Drumond, Gabriel Muricy Cunha, Marcia Sao Pedro Leal Souza, Ronaldo de Jesus, Sara A. Franco Guimaraes, Italo Coelho Nuno, Ian Carlos Brito de Santana, Jose Eduardo Ungar de Sa, George Roma Santos, Willadesmon Santos Silva, Thiago Ferreira Guedes, Emerson Luiz Lima Araujo, Rodrigo Fabiano do Carmo Said, Carlos Frederico Campelo de Albuquerque, Cassio Roberto Leonel Peterka, Alessandro Pecego Martins Romano, Rivaldo Venancio da Cunha, Ana Maria Bispo de Filippis, Arabela Leal e Silva de Mello, Marta Giovanetti, Luiz Carlos Junior Alcantara
Summary: Several studies have provided evidence of West Nile virus (WNV) circulation in Brazil, but the genomic diversity and transmission dynamics of the virus in the country are still largely unknown. Recent genomic monitoring activities in horses have revealed the presence of WNV in different regions of Brazil. This study retrospectively screened WNV samples from encephalitic horses and identified two independent introduction events of the virus in Brazil. These findings emphasize the importance of increasing the priority of WNV genomic monitoring in horses with encephalitis.
Article
Chemistry, Medicinal
Barbara Schroeder, Peter Demirel, Christina Fischer, Enaam Masri, Stephanie Kallis, Lisa Redl, Thomas Rudolf, Silke Bergemann, Christoph Arkona, Christoph Nitsche, Ralf Bartenschlager, Jorg Rademann
Summary: Viral proteases are crucial in virus replication, but there is still no antiviral therapy available for flaviviral infections. Nanoparticular antivirals, such as peptide-dextran conjugates, show promise in inhibiting viral replication at nontoxic concentrations and could be a new strategy for developing broad-spectrum antiflaviviral drugs.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Immunology
Haiyan Sun, Dhiraj Acharya, Amber M. Paul, Huafang Lai, Junyun He, Fengwei Bai, Qiang Chen
Summary: Researchers have developed a plant-based vaccine candidate that provides protective immunity against lethal West Nile virus and minimizes the risk of infection by Zika and dengue viruses.
Article
Plant Sciences
Anna T. Olek, Phillip S. Rushton, Daisuke Kihara, Peter Ciesielski, Uma K. Aryal, Zicong Zhang, Cynthia Stauffacher, Maureen C. McCann, Nicholas C. Carpita
Summary: This study investigated two plant-unique sequences in cellulose synthases and found that certain amino acid residues within these sequences play a crucial role in their function, while others do not.
Article
Microbiology
Mariana Leandro, Leandro Andrade, Luciano Vespoli, Julia Moreira, Vivian Pimentel, Fabiano Soares, Lucas Passamani, Vanildo Silveira, Goncalo de Souza Filho
Summary: This study investigated the key mechanisms of resistance to osmotic stress in Gluconacetobacter diazotrophicus. Proteomics analysis identified regulatory pathways for osmotic adjustment, de novo saturated fatty acids biosynthesis, and uptake of nutrients, while mutagenesis analysis showed the essential role of specific proteins in osmotolerance. The findings shed light on the importance of cell envelope and extracytoplasmic proteins for osmotolerance in this osmotolerant bacterium.
RESEARCH IN MICROBIOLOGY
(2021)
Article
Immunology
Junyun He, Huafang Lai, Adrian Esqueda, Qiang Chen
Summary: The study developed a VLP vaccine based on HBcAg displaying WNV Envelope protein wDIII, which showed high immunogenicity and potential as an effective, safe, and low-cost option for WNV vaccines.
Article
Pharmacology & Pharmacy
Tadahisa Teramoto, Kyung H. Choi, Radhakrishnan Padmanabhan
Summary: Flaviviruses, including dengue, West Nile, yellow fever, Japanese encephalitis, and Zika virus, are important human pathogens. These viruses cause a range of diseases, from mild symptoms to severe complications. Dengue infections have dramatically increased in recent decades, causing millions of infections and thousands of deaths each year. Zika virus and West Nile virus also pose significant threats to human health, especially to pregnant women and children.
ANTIVIRAL RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Nadia Mohamed Yusoff, Hasnah Osman, Mohd. Zaheen Hassan, Mohamed Ashraf Ali, Yeong Keng Yoon, Ezatul Ezleen Kamarulzaman, Muhammad Solehin Abd Ghani, Unang Supratman, Mohamad Nurul Azmi Mohamad Taib
Summary: The West Nile virus (WNV), a rapidly spreading flavivirus globally, lacks clinically approved drugs or vaccines. A series of spiropyrrolidine derivatives were synthesized and studied for their binding affinity to NS2B-NS3 protease, with one compound (5c) showing promising inhibition potential. This highlights the potential use of these compounds as drug candidates against WNV.
INDONESIAN JOURNAL OF CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Jana Skerlova, Jens Berndtsson, Hendrik Nolte, Martin Ott, Pal Stenmark
Summary: The pyruvate dehydrogenase complex (PDHc) is a multienzyme complex that converts pyruvate into acetyl-coenzyme A, linking glycolysis to the citric acid cycle. The core of PDHc is formed by dihydrolipoyl transacetylase, which provides binding sites for other enzymes and shuffles reaction intermediates between the active sites through covalently bound lipoyl domains. The cryo-EM structure of the E. coli dihydrolipoyl transacetylase core in a resting state reveals molecular details of the assembly and interactions at the active site.
NATURE COMMUNICATIONS
(2021)
Article
Biotechnology & Applied Microbiology
Nazia Thakur, Carina Conceicao, Ariel Isaacs, Stacey Human, Naphak Modhiran, Rebecca K. McLean, Miriam Pedrera, Tiong Kit Tan, Pramila Rijal, Alain Townsend, Geraldine Taylor, Paul R. Young, Daniel Watterson, Keith J. Chappell, Simon P. Graham, Dalan Bailey
Summary: In addition to viral entry into cells, viruses can also spread through cell-cell fusion, but the contribution of cell-cell fusion to viral pathogenesis is poorly understood at present.
JOURNAL OF GENERAL VIROLOGY
(2021)
Article
Multidisciplinary Sciences
Naphak Modhiran, Hao Song, Lidong Liu, Cheryl Bletchly, Lou Brillault, Alberto A. Amarilla, Xiaoying Xu, Jianxun Qi, Yan Chai, Stacey T. M. Cheung, Renee Traves, Yin Xiang Setoh, Summa Bibby, Connor A. P. Scott, Morgan E. Freney, Natalee D. Newton, Alexander A. Khromykh, Keith J. Chappell, David A. Muller, Katryn J. Stacey, Michael J. Landsberg, Yi Shi, George F. Gao, Paul R. Young, Daniel Watterson
Summary: The NS1 antibody 1G5.3 can effectively block NS1-mediated cell permeability of multiple flaviviruses, reduce viremia, and improve survival in various animal models. The protective effect of 1G5.3 is independent of effector function, making it a key site for broad-spectrum antiviral development.
Article
Immunology
Ariel Isaacs, Zheyi Li, Stacey T. M. Cheung, Danushka K. Wijesundara, Christopher L. D. McMillan, Naphak Modhiran, Paul R. Young, Charani Ranasinghe, Daniel Watterson, Keith J. Chappell
Summary: This study tested several adjuvants for their effectiveness in inducing humoral responses to influenza and RSV subunit vaccines in mice. While all adjuvants were able to induce potent neutralizing antibodies, none significantly increased the frequency of CD4(+) and CD8(+) IFN-γ(+) cells compared to unadjuvanted antigen. The varying responses to antigens with each adjuvant suggest that optimal adjuvant selection may depend on the specific antigen and desired immune response.
Review
Immunology
Christopher L. D. McMillan, Paul R. Young, Daniel Watterson, Keith J. Chappell
Summary: Current influenza virus vaccines mainly induce antibodies against the highly variable head domain of the hemagglutinin protein, but these antibodies are often strain-specific, resulting in limited cross-protection. Therefore, the annual update of vaccine formulations to counteract the challenge of influenza virus evolution is crucial.
Article
Multidisciplinary Sciences
Gayle K. McEwen, David E. Alquezar-Planas, Anisha Dayaram, Amber Gillett, Rachael Tarlinton, Nigel Mongan, Keith J. Chappell, Joerg Henning, Milton Tan, Peter Timms, Paul R. Young, Alfred L. Roca, Alex D. Greenwood
Summary: The study reveals that the integration sites of Koala retrovirus cluster near known cancer genes and show a high mutational load associated with the virus's germline invasion.
Koalas are prone to neoplasms when infected, with a high mutational load during virus germline invasion.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Alberto A. Amarilla, Naphak Modhiran, Yin Xiang Setoh, Nias Y. G. Peng, Julian D. J. Sng, Benjamin Liang, Christopher L. D. McMillan, Morgan E. Freney, Stacey T. M. Cheung, Keith J. Chappell, Alexander A. Khromykh, Paul R. Young, Daniel Watterson
Summary: The article introduces the iPA detection method, utilizing multiple antibodies and dual-specificity probe antibodies for detecting SARS-CoV-2, and demonstrates its use for high-throughput viral titration and neutralization assays within 24 hours, with compatibility in a 384-well format.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Alberto A. Amarilla, Julian D. J. Sng, Rhys Parry, Joshua M. Deerain, James R. Potter, Yin Xiang Setoh, Daniel J. Rawle, Thuy T. Le, Naphak Modhiran, Xiaohui Wang, Nias Y. G. Peng, Francisco J. Torres, Alyssa Pyke, Jessica J. Harrison, Morgan E. Freney, Benjamin Liang, Christopher L. D. McMillan, Stacey T. M. Cheung, Darwin J. Da Costa Guevara, Joshua M. Hardy, Mark Bettington, David A. Muller, Fasseli Coulibaly, Frederick Moore, Roy A. Hall, Paul R. Young, Jason M. Mackenzie, Jody Hobson-Peters, Andreas Suhrbier, Daniel Watterson, Alexander A. Khromykh
Summary: The study shows that a simplified reverse genetics method can efficiently assemble infectious full-length cDNA, enabling easier in vitro and in vivo characterization of viruses like SARS-CoV-2.
NATURE COMMUNICATIONS
(2021)
Article
Virology
Ariel Isaacs, Stacey T. M. Cheung, Nazia Thakur, Noushin Jaberolansar, Andrew Young, Naphak Modhiran, Dalan Bailey, Simon P. Graham, Paul R. Young, Keith J. Chappell, Daniel Watterson
Summary: The majority of vaccine development for Nipah virus (NiV) and respiratory syncytial virus (RSV) focuses on their attachment and fusion proteins. Utilizing a vaccine strategy that includes both the F and G proteins can provide broader protection against these pathogens.
Article
Multidisciplinary Sciences
Christopher L. D. McMillan, Jovin J. Y. Choo, Adi Idris, Aroon Supramaniam, Naphak Modhiran, Alberto A. Amarilla, Ariel Isaacs, Stacey T. M. Cheung, Benjamin Liang, Helle Bielefeldt-Ohmann, Armira Azuar, Dhruba Acharya, Gabrielle Kelly, Germain J. P. Fernando, Michael J. Landsberg, Alexander A. Khromykh, Daniel Watterson, Paul R. Young, Nigel A. J. McMillan, David A. Muller
Summary: The study demonstrates the use of high-density microarray patch (HD-MAP) for delivering a SARS-CoV-2 spike subunit vaccine directly to the skin, showing that the vaccine is stable on the patches and enhances both cellular and antibody immune responses. Furthermore, antibodies elicited by the vaccine can potently neutralize clinically relevant isolates including the Alpha and Beta variants, providing complete protection in a mouse model with a single dose of the HD-MAP-delivered spike vaccine.
Article
Immunology
Christopher L. D. McMillan, Stacey T. M. Cheung, Naphak Modhiran, James Barnes, Alberto A. Amarilla, Helle Bielefeldt-Ohmann, Leo Yi Yang Lee, Kate Guilfoyle, Geert van Amerongen, Koert Stittelaar, Virginie Jakon, Celia Lebas, Patrick Reading, Kirsty R. Short, Paul R. Young, Daniel Watterson, Keith J. Chappell
Summary: Influenza viruses cause a significant number of infections and deaths annually. Development of a universal influenza vaccine is challenging, but a modular trimerization domain known as the molecular clamp shows promise for rapid response vaccine development. The clamp-stabilised HA proteins demonstrate cross protection and serve as a proof-of-concept for future pandemic response vaccines.
Article
Immunology
Ahmed O. Shalash, Armira Azuar, Harrison Y. R. Madge, Naphak Modhiran, Alberto A. Amarilla, Benjamin Liang, Alexander A. Khromykh, Daniel Watterson, Paul R. Young, Istvan Toth, Mariusz Skwarczynski
Summary: This protocol describes a method for accurate measurement of SARS-CoV-2 spike protein-RBD neutralization efficacy using murine immune serum. It employs a simple ELISA technique with key steps including serum heat treatment, blank controls, optimal ACE2 addition, and mechanistically derived neutralization calculation. The protocol can be completed in 16 hours for >30 serum samples and is considered a valuable asset for initial vaccine development stages.
Article
Immunology
Jovin J. Y. Choo, Christopher L. D. McMillan, Germain J. P. Fernando, Roy A. Hall, Paul R. Young, Jody Hobson-Peters, David A. Muller
Summary: The HD-MAP provides stable delivery of vaccines through dry coating, and HSA has been identified as the leading stabilizing excipient. Vaccines stored on HD-MAP at 4°C for a month maintained vaccine potency and demonstrated high recovery rate.
Article
Pharmacology & Pharmacy
Ahmed O. Shalash, Armira Azuar, Harrison Y. R. Madge, Naphak Modhiran, Alberto A. Amarilla, Benjamin Liang, Alexander A. Khromykh, Waleed M. Hussein, Keith J. Chappell, Daniel Watterson, Paul R. Young, Mariusz Skwarczynski, Istvan Toth
Summary: The SARS-CoV-2 virus has caused a global crisis with billions of infections and millions of deaths. Current DNA and mRNA vaccines have shown decreased efficacy over time, especially the Pfizer BNT162 vaccine. Variant strains have further reduced vaccine effectiveness. Peptide vaccines offer an alternative solution with greater stability and flexibility to target emerging strains.
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)