Article
Biotechnology & Applied Microbiology
Vengala Rao Yenuganti, Sumbul Afroz, Rafiq Ahmad Khan, Chandrima Bharadwaj, Deepti Kailash Nabariya, Nagaraj Nayak, Madhuri Subbiah, Kumaraswami Chintala, Sharmistha Banerjee, Pallu Reddanna, Nooruddin Khan
Summary: This study demonstrates the antiviral properties of milk exosomes and opens new avenues for the development of exosome-based therapies to treat viral diseases.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Immunology
Yi-Ling Cheng, Chiao-Hsuan Chao, Yen-Chung Lai, Kun-Han Hsieh, Jen-Ren Wang, Shu-Wen Wan, Hong-Jyun Huang, Yung-Chun Chuang, Woei-Jer Chuang, Trai-Ming Yeh
Summary: This study confirms the presence of antibodies related to SARS-CoV-2 in dengue virus patients, and these antibodies can cross-react with proteins of the dengue virus. These antibodies can inhibit the pathological reactions caused by dengue virus infection, potentially providing some level of protection against dengue virus.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Md. Mahbubur Rahman, Sourav Biswas, Kazi Jahidul Islam, Archi Sundar Paul, Shiplob Kumar Mahato, Md. Ackas Ali, Mohammad A. Halim
Summary: The study focused on finding potential inhibitors against the NS3 protease of the dengue virus through systematic screening. Among 40 antiviral phytochemicals, Cyanidin 3-Glucoside, Dithymoquinone, and Glabridin were predicted to be potent inhibitors based on their binding affinity. The ligand-protein complexes were further analyzed through molecular dynamics simulation and binding free energy calculation to investigate their binding stability, indicating potential effectiveness of these inhibitors.
COMPUTERS IN BIOLOGY AND MEDICINE
(2021)
Article
Immunology
Tomohiro Kotaki, Yurie Nagai, Atsushi Yamanaka, Eiji Konishi, Masanori Kameoka
Summary: This study focused on developing a Japanese encephalitis (JE) vaccine that does not induce antibody-dependent enhancement (ADE) of dengue virus (DENV) infection. By introducing a mutation at the 106th amino acid residue of the JEV E protein, the modified JE vaccine was able to significantly reduce the production of cross-reactive ADE-prone antibodies against DENV.
Article
Immunology
Sua Lee, Shina Jang, Jihoon Kang, Soo Bin Park, Young Woo Han, Hyemi Nam, Munkyung Kim, Jeewon Lee, Ki Joon Cho, Jeonghun Kim, Miyoung Oh, Jihye Ryu, Jong Hyeon Seok, Yunhwa Kim, Jee-Boong Lee, Man-Seong Park, Yong-Sung Kim, Hosun Park, Dong-Sik Kim
Summary: A universal SARS-CoV-2 neutralizing antibody, MG1141A, was developed in this study, which effectively neutralizes live viruses and retains its activity against various variants of SARS-CoV-2, contributing to the development of a novel antibody therapeutic approach.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Xilin Wu, Lin Cheng, Ming Fu, Bilian Huang, Linjing Zhu, Shijie Xu, Haixia Shi, Doudou Zhang, Huanyun Yuan, Waqas Nawaz, Ping Yang, Qinxue Hu, Yalan Liu, Zhiwei Wu
Summary: Neutralizing nanobodies derived from an alpaca immunized with SARS-CoV-2 spike glycoprotein show potential therapeutic effects against COVID-19. A trimer of Nbs, Nb-15-NbH-Nb-15, exhibits high neutralization potency against SARS-CoV-2 live virus and variants with a long half-life. Intranasal administration of Nb-15-Nb-H-Nb-15 provides effective protection against SARS-CoV-2 infection in transgenic hACE2 mice for both prophylactic and therapeutic purposes.
Article
Biochemistry & Molecular Biology
Jennifer M. Zupancic, Alec A. Desai, John S. Schardt, Ghasidit Pornnoppadol, Emily K. Makowski, Matthew D. Smith, Andrew A. Kennedy, Mayara Garcia de Mattos Barbosa, Marilia Cascalho, Thomas M. Lanigan, Andrew W. Tai, Peter M. Tessier
Summary: There is a strong interest in developing effective methods for generating neutralizing antibodies and nanobodies against SARS-CoV-2. This study presents a simple directed evolution method for producing nanobodies with high affinities and neutralization activities, which can effectively neutralize both SARS-CoV-2 pseudovirus and live virus.
CELL CHEMICAL BIOLOGY
(2021)
Article
Virology
Rong Wang, Jiansheng Lu, Lei Chen, Yunzhou Yu, Zhixin Yang
Summary: In this study, a bispecific antibody LUZ-8F2?6B1 was engineered to display potent neutralization activity against four serotypes of DENV, providing protection in a mouse model. Additionally, deletion of nine amino acids in the Fc region abolished antibody-dependent enhancement at lower doses, making LUZ-8F2?6B1 a promising, safe, and effective agent for prophylaxis and treatment of DENV infection.
Article
Public, Environmental & Occupational Health
Surachet Benjathummarak, Atsushi Yamanaka, Thanyaluk Krasae, Chonlatip Pipattanaboon, Subenya Injampa, Pannamthip Pitaksajjakul, Pongrama Ramasoota
Summary: This study successfully evaluated the expression of DNA plasmid-harboring modified antibody gene that produces neutralizing human monoclonal antibodies against four serotypes of dengue virus without enhancing activity in BALB/c mice. The modified antibodies showed cross-neutralization to all four DENV serotypes, making it a possible therapeutic antibody candidate against DENV infection.
ASIAN PACIFIC JOURNAL OF TROPICAL MEDICINE
(2021)
Article
Biotechnology & Applied Microbiology
Qianlin Li, Fuqiang Zhang, Yi Lu, Huan Hu, Jin Wang, Cheng Guo, Qiang Deng, Conghui Liao, Qin Wu, Tingsong Hu, Zeliang Chen, Jiahai Lu
Summary: In this study, we developed potent multivalent VHH antibodies targeting the E2 glycoprotein of CHIKV, with Nb-2E8 and Nb-3C5 showing high-affinity binding within the nanomolar range.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Review
Immunology
Vincent Dussupt, Kayvon Modjarrad, Shelly J. Krebs
Summary: The unprecedented Zika outbreak in the Americas from 2015-2016 led to global concern and accelerated the deployment of vaccine and therapeutic countermeasures. Several potent neutralizing antibodies against Zika and related flaviviruses have been discovered in recent years. Structure-based approaches have helped identify species-specific and cross-protective epitopes with therapeutic value.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Virology
Anais Broban, Marie-Marie Olive, Michael Luciano Tantely, Anne-Claire Dorsemans, Fanjasoa Rakotomanana, Jean-Pierre Ravalohery, Christophe Rogier, Jean-Michel Heraud, Soa Fy Andriamandimby
Summary: This study estimated the seroprevalence of three arboviruses (dengue, chikungunya, and West Nile) in Madagascar and identified risk factors associated with seropositivity. The results showed that 6.5% were seropositive for dengue virus, 13.7% for chikungunya virus, and 12.7% for West Nile virus. Dengue and chikungunya viruses were recently introduced, with higher prevalence in the eastern and northern parts of the country, while West Nile virus circulated in all regions. Factors such as vegetation cover, forest work, cultivated areas, and standard of living were associated with seropositivity.
Article
Chemistry, Medicinal
Md Ashraf-Uz-Zaman, Xin Li, Yuan Yao, Chandra Bhushan Mishra, Bala Krishna Moku, Yongcheng Song
Summary: Dengue (DENV) and Zika (ZIKV) viruses are significant human pathogens, causing about 100 million symptomatic infections annually. These infections lead to a higher incidence of serious neurological diseases, such as microcephaly and Guillain-Barre syndrome. A study identified 2,3,6-trisubstituted quinazolinone compounds as novel inhibitors of ZIKV replication. Several analogues were synthesized and tested, and compounds 22, 27, and 47 showed potent activities against ZIKV and DENV with low cytotoxicity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Microbiology
Jisang Park, Ju Kim, Yong-Suk Jang
Summary: Dengue virus is a mosquito-borne virus that causes dengue fever, and its cases have significantly increased in the past two decades. Currently, there is only one available vaccine with age restrictions. Researchers are actively working on developing effective vaccines and understanding the viral antigen configuration.
JOURNAL OF MICROBIOLOGY
(2022)
Review
Medicine, Research & Experimental
Wen-Hung Wang, Aspiro Nayim Urbina, Chih-Yen Lin, Zih-Syuan Yang, Wanchai Assavalapsakul, Arunee Thitithanyanont, Po-Liang Lu, Yen-Hsu Chen, Sheng-Fan Wang
Summary: The development of dengue vaccines is crucial in preventing and controlling the global health threat caused by Dengue virus. Current approved vaccines have demonstrated low efficacy in certain populations, leading to ongoing investigation and development of novel strategies for dengue vaccines.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Immunology
Sheila F. Lumley, Gillian Rodger, Bede Constantinides, Nicholas Sanderson, Kevin K. Chau, Teresa L. Street, Denise O'Donnell, Alison Howarth, Stephanie B. Hatch, Brian D. Marsden, Stuart Cox, Tim James, Fiona Warren, Liam J. Peck, Thomas G. Ritter, Zoe de Toledo, Laura Warren, David Axten, Richard J. Cornall, E. Yvonne Jones, David Stuart, Gavin Screaton, Daniel Ebner, Sarah Hoosdally, Meera Chand, Derrick W. Crook, Anne-Marie O'donnell, Christopher P. Conlon, Koen B. Pouwels, A. Sarah Walker, Tim E. A. Peto, Susan Hopkins, Timothy M. Walker, Nicole E. Stoesser, Philippa C. Matthews, Katie Jeffery, David W. Eyre
Summary: Natural infection with detectable anti-spike antibodies and two doses of vaccine provide robust protection against SARS-CoV-2 infection, including the B.1.1.7 variant in healthcare workers. Single dose vaccination significantly reduces the risk of symptomatic infection.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Wanwisa Dejnirattisai, Jiandong Huo, Daming Zhou, Jiri Zahradnik, Piyada Supasa, Chang Liu, Helen M. E. Duyvesteyn, Helen M. Ginn, Alexander J. Mentzer, Aekkachai Tuekprakhon, Rungtiwa Nutalai, Beibei Wang, Aiste Dijokaite, Suman Khan, Ori Avinoam, Mohammad Bahar, Donal Skelly, Sandra Adele, Sile Ann Johnson, Ali Amini, Thomas G. Ritter, Chris Mason, Christina Dold, Daniel Pan, Sara Assadi, Adam Bellass, Nicola Omo-Dare, David Koeckerling, Amy Flaxman, Daniel Jenkin, Parvinder K. Aley, Merryn Voysey, Sue Ann Costa Clemens, Felipe Gomes Naveca, Valdinete Nascimento, Fernanda Nascimento, Cristiano Fernandes da Costa, Paola Cristina Resende, Alex Pauvolid-Correa, Marilda M. Siqueira, Vicky Baillie, Natali Serafin, Gaurav Kwatra, Kelly Da Silva, Shabir A. Madhi, Marta C. Nunes, Tariq Malik, Peter J. M. Openshaw, J. Kenneth Baillie, Malcolm G. Semple, Alain R. Townsend, Kuan-Ying A. Huang, Tiong Kit Tan, Miles W. Carroll, Paul Klenerman, Eleanor Barnes, Susanna J. Dunachie, Bede Constantinides, Hermione Webster, Derrick Crook, Andrew J. Pollard, Teresa Lambe, Neil G. Paterson, Mark A. Williams, David R. Hall, Elizabeth E. Fry, Juthathip Mongkolsapaya, Jingshan Ren, Gideon Schreiber, David Stuart, Gavin R. Screaton
Summary: On November 24, 2021, the sequence of a new SARS-CoV-2 variant, Omicron-B.1.1.529, was announced. Compared to previous variants, Omicron has a higher number of mutations in the Spike (S) protein. Serum neutralization of Omicron by individuals vaccinated or previously infected with Alpha, Beta, Gamma, or Delta variants is significantly reduced or ineffective. Third vaccine doses can boost neutralization titers against Omicron, and high titers are observed in both vaccinated individuals and those infected with the Delta variant. Most potent monoclonal antibodies and antibodies under development are unable to effectively neutralize Omicron due to mutations in its Spike protein. Omicron has structural changes compared to earlier viruses and utilizes mutations that enhance its binding to ACE2, allowing for immune escape. This results in a large number of mutations in the ACE2 binding site and a rebalancing of receptor affinity similar to earlier pandemic viruses.
Article
Microbiology
Chang Liu, Daming Zhou, Rungtiwa Nutalai, Helen M. E. Duyvesteyn, Aekkachai Tuekprakhon, Helen M. Ginn, Wanwisa Dejnirattisai, Piyada Supasa, Alexander J. Mentzer, Beibei Wang, James Brett Case, Yuguang Zhao, Donal T. Skelly, Rita E. Chen, Sile Ann Johnson, Thomas G. Ritter, Chris Mason, Tariq Malik, Nigel Temperton, Neil G. Paterson, Mark A. Williams, David R. Hall, Daniel K. Clare, Andrew Howe, Philip J. R. Goulder, Elizabeth E. Fry, Michael S. Diamond, Juthathip Mongkolsapaya, Jingshan Ren, David Stuart, Gavin R. Screaton
Summary: This study investigated several variants of SARS-CoV-2 and found that the Beta variant has the largest antigenic difference compared to other variants, such as Delta, and is poorly neutralized by serum from early pandemic and Delta viruses. The study also revealed that certain antibodies can recognize conserved neutralizing epitopes, while others target specific mutated residues in the Beta variant.
CELL HOST & MICROBE
(2022)
Article
Biochemistry & Molecular Biology
Xiaodi Yu, Tina-Marie Mullen, Vahid Abrishami, Juha T. Huiskonen, Glen R. Nemerow, Vijay S. Reddy
Summary: This passage discusses the maturation process of adenoviruses, focusing on the proteolytic processing of various proteins and the subsequent reorganization of the virus core. It highlights the preliminary structures of several precursor proteins, as well as the potential co-assembly of hexons with certain protein precursors. The findings suggest a complex interplay between different forms of proteins during the processing and release from the hexon cavities.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hannah T. Baddock, Sanja Brolih, Yuliana Yosaatmadja, Malitha Ratnaweera, Marcin Bielinski, Lonnie P. Swift, Abimael Cruz-Migoni, Haitian Fan, Jeremy R. Keown, Alexander P. Walker, Garrett M. Morris, Jonathan M. Grimes, Ervin Fodor, Christopher J. Schofield, Opher Gileadi, Peter J. McHugh
Summary: The nsp14-nsp10 complex of SARS-CoV-2 has been found to possess RNase activity and is capable of digesting various RNA structures. Its activity is enhanced by the viral RNA-dependent RNA polymerase complex nsp12-7-8. Inhibitors of nsp14-nsp10, including ebselen and raltegravir, have been identified and may have potential use in the treatment of COVID-19.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
John J. Kelly, Dale Tranter, Els Pardon, Gamma Chi, Holger Kramer, Lotta Happonen, Kelly M. Knee, Jay M. Janz, Jan Steyaert, Christine Bulawa, Ville O. Paavilainen, Juha T. Huiskonen, Wyatt W. Yue
Summary: The integrity of a cell's proteome relies on the correct folding of polypeptides, which is facilitated by the chaperonin TCP-1 ring complex (TRiC). Structural studies have provided insights into the architecture and substrate recognition of TRiC, but the fate of substrates inside the TRiC chamber has remained unclear. In this study, cryo-EM was used to determine the structure of endogenous human TRiC with substrates and cochaperone at different folding stages. The findings revealed the positioning of already-folded regions of client proteins at the chamber wall, allowing unstructured regions to achieve their native fold. The substrates engaged with different sections of the chamber during the folding process, while the cochaperone PhLP2A acted as a molecular strut between the substrate and TRiC chamber. These structural snapshots contribute to our understanding of client protein folding within TRiC.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Microbiology
Tessa Prince, Xiaofeng Dong, Rebekah Penrice-Randal, Nadine Randle, Catherine Hartley, Hannah Goldswain, Benjamin Jones, Malcolm G. Semple, J. Kenneth Baillie, Peter J. M. Openshaw, Lance Turtle, Grant L. Hughes, Enyia R. Anderson, Edward Patterson, Julian Druce, Gavin Screaton, Miles W. Carroll, James P. Stewart, Julian A. Hiscox
Summary: New variants of SARS-CoV-2 are continuously emerging. Understanding virus evolution and selection pressures requires considering population dynamics and new variants.
Article
Medicine, General & Internal
Alexandra J. Spencer, Susan Morris, Marta Ulaszewska, Claire Powers, Reshma Kailath, Cameron Bissett, Adam Truby, Nazia Thakur, Joseph Newman, Elizabeth R. Allen, Indra Rudiansyah, Chang Liu, Wanwisa Dejnirattisai, Juthathip Mongkolsapaya, Hannah Davies, Francesca R. Donnellan, David Pulido, Thomas P. Peacock, Wendy S. Barclay, Helen Bright, Kuishu Ren, Gavin Screaton, Patrick McTamney, Dalan Bailey, Sarah C. Gilbert, Teresa Lambe
Summary: This study describes the generation and preclinical assessment of a vaccine targeting Beta VoC (B.1.351), which shows immunogenicity after a single dose and produces antibody responses to other variants as a booster, along with a strong T cell response.
Article
Medicine, Research & Experimental
Anna L. McNaughton, Robert S. Paton, Matthew Edmans, Jonathan Youngs, Judith Wellens, Prabhjeet Phalora, Alex Fyfe, Sandra Belij-Rammerstorfer, Jai S. Bolton, Jonathan Ball, George W. Carnell, Wanwisa Dejnirattisai, Christina Dold, David W. Eyre, Philip Hopkins, Alison Howarth, Kreepa Kooblall, Hannah Klim, Susannah Leaver, Lian Ni Lee, Cesar Lopez-Camacho, Sheila F. Lumley, Derek C. Macallan, Alexander J. Mentzer, Nicholas M. Provine, Jeremy Ratcliff, Jose Slon-Compos, Donal Skelly, Lucas Stolle, Piyada Supasa, Nigel Temperton, Chris Walker, Beibei Wang, Duncan Wyncoll, Peter Simmonds, Teresa Lambe, John Kenneth Baillie, Malcolm G. Semple, Peter J. M. Openshaw, Uri Obolski, Marc Turner, Miles Carroll, Juthathip Mongkolsapaya, Gavin Screaton, Stephen H. Kennedy, Lisa Jarvis, Eleanor Barnes, Susanna Dunachie, Jose Lourenco, Philippa C. Matthews, Tihana Bicanic, Paul Klenerman, Sunetra Gupta, Craig P. Thompson
Summary: The immune response to the SARS-CoV-2 virus in fatal COVID-19 cases is enriched for antibodies that target epitopes shared with other endemic coronaviruses, rather than the more protective regions of the virus. This response is correlated with the magnitude of antibody responses to the spike protein of both SARS-CoV-2 and other beta-coronaviruses in individuals admitted to the ICU with fatal outcomes. However, there is no significant difference in antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid between fatal and nonfatal cases.
Article
Multidisciplinary Sciences
Tommi Kotila, Hugo Wioland, Muniyandi Selvaraj, Konstantin Kogan, Lina Antenucci, Antoine Jegou, Juha T. Huiskonen, Guillaume Romet-Lemonne, Pekka Lappalainen
Summary: The authors report the structure and function analysis of highly divergent actin from Leishmania parasite. The study reveals the rapid dynamics and molecular basis of parasite actin, providing insight into the evolution of the actin cytoskeleton. The findings show how divergent parasites achieve rapid actin dynamics using a simple set of actin-binding proteins, elucidating the evolution of the actin cytoskeleton.
NATURE COMMUNICATIONS
(2022)
Article
Critical Care Medicine
Robert H. Shaw, Xinxue Liu, Arabella S. Stuart, Melanie Greenland, Parvinder K. Aley, Nick J. Andrews, J. Claire Cameron, Sue Charlton, Elizabeth A. Clutterbuck, Andrea M. Collins, Wanwisa Dejnirattisai, Tanya Dinesh, Saul N. Faust, Daniela M. Ferreira, Adam Finn, Christopher A. Green, Bassam Hallis, Paul T. Heath, Helen Hill, Teresa Lambe, Rajeka Lazarus, Vincenzo Libri, Fei Long, Yama F. Mujadidi, Emma L. Plested, Ella R. Morey, Samuel Provstgaard-Morys, Maheshi N. Ramasamy, Mary Ramsay, Robert C. Read, Hannah Robinson, Gavin R. Screaton, Nisha Singh, David P. J. Turner, Paul J. Turner, Iason Vichos, Laura L. Walker, Rachel White, Jonathan S. Nguyen-Van-Tam, Matthew D. Snape
Summary: This study conducted exploratory analyses on the priming intervals of COVID-19 vaccines and found that longer intervals can reduce reactogenicity for the BNT162b2 vaccine as the second dose and enhance humoral immunogenicity in homologous priming schedules, but result in overall lower T-cell responses across all schedules. These findings support the flexibility of priming intervals in COVID-19 vaccine schedules.
LANCET RESPIRATORY MEDICINE
(2022)
Article
Medicine, Research & Experimental
Laura Giorgi, Akseli Niemela, Esa-Pekka Kumpula, Ossi Natri, Petteri Parkkila, Juha T. Huiskonen, Artturi Koivuniemi
Summary: This study combines coarse-grained molecular dynamics simulations with complementary experiments to gain mechanistic insight into how apoA-I mimetic peptide 22A and its variants tune LCAT activity in peptide-lipid nanodiscs. Results show that peptide 22A forms transient antiparallel dimers at the rim of nanodiscs, and the removal of C-terminal lysine K22 decreases dimerization tendency and LCAT activity. Furthermore, simulations reveal that LCAT localizes preferentially to the rim of nanodiscs in a manner that shields important domains from water phase, and the conformation of LCAT in the rim affects its activity.
MOLECULAR PHARMACEUTICS
(2022)
Article
Cell Biology
Muniyandi Selvaraj, Shrikant B. Kokate, Gabriella Reggiano, Konstantin Kogan, Tommi Kotila, Elena Kremneva, Frank DiMaio, Pekka Lappalainen, Juha T. Huiskonen
Summary: The actin cytoskeleton plays a critical role in various cellular processes. Tropomyosins are important proteins that regulate actin filaments. This study reveals the molecular mechanisms of how different tropomyosin isoforms interact with actin filaments, leading to their differential functions in myosin II activation and protection against ADF/cofilin-catalyzed severing.
Article
Biochemical Research Methods
Jack D. Whitehead, Jonathan M. Grimes, Jeremy R. Keown
Summary: Bornaviruses are RNA viruses that infect a wide range of hosts including mammals, reptiles, and birds. This study presents the structure of the oligomerization domain of the phosphoprotein, which is an important component of the bornavirus replication complex. The findings provide valuable insights into the assembly process of the phosphoprotein and its role in viral replication.
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2023)
Meeting Abstract
Biophysics
Tommi Kotila, Hugo Wioland, Selvaraj Muniyandi, Konstantin Kogan, Lina Antenucci, Antoine G. Jegou, Juha Huiskonen, Guillaume Romet-Lemonne, Pekka Lappalainen
BIOPHYSICAL JOURNAL
(2022)