Review
Biochemistry & Molecular Biology
Gregory Mathez, Valeria Cagno
Summary: The majority of antivirals target viral proteins, but RNA is gaining attention as a new and promising antiviral target. This article discusses methods for identifying RNA-targeting compounds, including determination of RNA structures and in silico screening. It also reviews small molecules that target specific RNA elements in viruses like SARS-CoV-2 and HIV.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Virology
Verena Battisti, Ernst Urban, Thierry Langer
Summary: Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes chikungunya fever (CHIKF) characterized by severe joint pain and myalgia. With no effective antiviral drugs or vaccines currently available, the development of a drug to inhibit CHIKV is crucial for CHIKF treatment. Various approaches for identifying potential compounds and promising viral and host targets are discussed in current antiviral research and development.
Article
Virology
Mona Teppor, Eva Zusinaite, Andres Merits
Summary: Phosphorylation of nsP3 in CHIKV plays a crucial role in its replicase activity and virus infectivity, with mutations leading to attenuation and complete loss of viral activity. The unique distribution of phosphorylation sites in the HVD of nsP3 distinguishes CHIKV from other alphaviruses like SFV and SINV, highlighting the potential of targeting phosphorylation as a strategy for antiviral therapy and CHIKV attenuation.
JOURNAL OF VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Irina Malinova, Arkadiusz Zupok, Amid Massouh, Mark Aurel Schoettler, Etienne H. Meyer, Liliya Yaneva-Roder, Witold Szymanski, Margit Roessner, Stephanie Ruf, Ralph Bock, Stephan Greiner
Summary: The study reveals the presence of translational recoding mechanism in chloroplasts, which can correct frameshift mutations and restore photoautotrophic growth in the presence of mutations that would otherwise be lethal.
Article
Biochemistry & Molecular Biology
Vitor Won-Held Rabelo, Izabel Christina Nunes de Palmer Paixao, Paula Alvarez Abreu
Summary: This study investigated the structural basis for inhibiting the CHIKV nsP2 protease using molecular docking and dynamics simulations. The results showed that trans isomers, but not cis ones, bound close to the catalytic dyad, which may explain the isomerism requirements for enzyme inhibition. The binding mode analyses of other known inhibitors revealed highly conserved contacts between inhibitors and specific enzyme residues. Molecular dynamics simulations highlighted the importance of nonpolar interactions as the main forces for inhibitor binding. True inhibitors exhibited lower structural fluctuation, higher ligand efficiency, and did not induce significant changes in protein correlated motions.
JOURNAL OF MOLECULAR MODELING
(2022)
Article
Pharmacology & Pharmacy
Yaw Bia Tan, Michelle Cheok Yien Law, Dahai Luo
Summary: This article discusses the assembly and function of the virus RC, and highlights its potential as a multi-enzyme target for developing antiviral drugs. It also suggests that the alphavirus RC has therapeutic potential through self-amplifying RNA technology for both infectious and non-infectious diseases.
ANTIVIRAL RESEARCH
(2023)
Article
Virology
Sainan Wang, Andres Merits
Summary: This study demonstrates the importance of the interaction between G3BPs and nsP2 in CHIKV RNA replication and the ability of nsP2 to restore the infectivity of mutant viruses lacking G3BP-binding motifs in nsP3's HVD.
JOURNAL OF VIROLOGY
(2022)
Article
Immunology
Christin Schmidt, Florian D. Hastert, Julia Gerbeth, Tim Beissert, Ugur Sahin, Mario Perkovic, Barbara S. Schnierle
Summary: The study demonstrated that a CHIKV vaccine candidate based on trans-amplifying RNA can induce CHIKV- and RRV-specific immune responses in mice. However, higher antibody titers and neutralization capacity were observed after immunization with a single TR-RNA. There was no significant difference in alphavirus-specific T cell responses between bivalent and single vaccinations.
Article
Plant Sciences
Sze Mun Chan, Kong Soo Khoo, Shamala Devi Sekaran, Nam Weng Sit
Summary: The study evaluated 132 extracts from 21 medicinal plants for anti-chikungunya virus activity, identifying several plant extracts with potential to inhibit viral infection.
Article
Immunology
Shambhavi Rao, Eranga Abeyratne, Joseph R. Freitas, Chenying Yang, Kothila Tharmarajah, Helen Mostafavi, Xiang Liu, Mehfuz Zaman, Suresh Mahalingam, Ali Zaid, Adam Taylor
Summary: Our study shows that using a gene delivery system could enhance the efficacy of live-attenuated vaccines encoded with a gene to prevent severe arthritic disease. The experiments conducted on mice demonstrate that this vaccine can provide long-lasting immune protection and has a systemic protective effect against CHIKV disease.
Article
Virology
Amrita Saha, Badri Narayan Acharya, Manmohan Parida, Nandita Saxena, Jaya Rajaiya, Paban Kumar Dash
Summary: DCR 137 has been identified as a potential candidate for inhibiting the replication of CHIKV and Ross River virus, showing stronger antiviral activity compared to traditional drugs.
Article
Virology
Vitor Won-Held Rabelo, Veronica Diniz da Silva, Maria Leonisa Sanchez Nunez, Leonardo dos Santos Correa Amorim, Camilla Djenne Buarque, Richard J. Kuhn, Paula Alvarez Abreu, Izabel Christina Nunes de Palmer Paixao
Summary: This study found that two 1,2,3-triazole derivatives exhibit antiviral activity against Chikungunya virus. Compound 2 inhibits virus entry, while compound 1 inhibits virus release.
Review
Immunology
Dali Han, Meng Michelle Xu
Summary: Characterization of RNA modifications has led to the identification of their distribution features and molecular functions. The dynamic changes in RNA modification play a critical role in the development and function of the immune system. This review discusses the value of innovative RNA modification profiling technologies in understanding the diverse and dynamic functions of these modifications in immune cells within healthy and diseased contexts, as well as exploring the mechanisms by which aberrant RNA modifications modulate the immune milieu of the tumor microenvironment.
ANNUAL REVIEW OF IMMUNOLOGY
(2023)
Review
Chemistry, Multidisciplinary
Shalakha Hegde, Zhichao Tang, Junxing Zhao, Jingxin Wang
Summary: The ongoing COVID-19 pandemic has had a significant impact on global public health and society, with research on targeting conserved SARS-CoV-2 RNA structures and sequences emerging as a promising new approach to inhibit viral infection. These RNA-targeting molecules could serve as an emerging class of antiviral drug candidates for future viral outbreaks.
FRONTIERS IN CHEMISTRY
(2021)
Review
Cardiac & Cardiovascular Systems
Andreas B. Gevaert, Nathanael Wood, Jente R. A. Boen, Constantinos H. Davos, Dominique Hansen, Henner Hanssen, Guido Krenning, Trine Moholdt, Elena Osto, Francesco Paneni, Roberto F. E. Pedretti, Torsten Plosch, Maria Simonenko, T. Scott Bowen
Summary: This article discusses the link between changes in epigenetic systems and cardiovascular disease, as well as the acute and chronic effects of physical activity and dietary changes on epigenetics. It proposes exercise and nutrition as potential triggers for epigenetic signals that can reshape the transcriptional programs affecting CVD phenotypes.
EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
(2022)
Article
Virology
Bibha Dahal, Shih-Chao Lin, Brian D. Carey, Jonathan L. Jacobs, Jonathan D. Dinman, Monique L. van Hoek, Andre A. Adams, Kylene Kehn-Hall
Review
Biochemistry & Molecular Biology
Vivek M. Advani, Pavel Ivanov
CELLULAR AND MOLECULAR LIFE SCIENCES
(2020)
Article
Immunology
Rezia Era Braza, Aliyah B. Silver, Ganesh S. Sundar, Sarah E. Davis, Afrooz Razi, Emrul Islam, Meaghan Hart, Jinyi Zhu, Yoann Le Breton, Kevin S. McIver
INFECTION AND IMMUNITY
(2020)
Article
Biochemistry & Molecular Biology
Jamie A. Kelly, Alexandra N. Olson, Krishna Neupane, Sneha Munshi, Josue San Emeterio, Lois Pollack, Michael T. Woodside, Jonathan D. Dinman
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Multidisciplinary Sciences
Joseph A. Kendra, Kentaro Tohma, Lauren A. Ford-Siltz, Cara J. Lepore, Gabriel Parra
Summary: Noroviruses, especially the GII.4 genotype, are the main cause of acute gastroenteritis. Antigenic analysis on a virus-like particle panel representing major chronological GII.4 variants shows complex genetic determinants associated with antigenic diversification. Multiple coevolving amino acid changes, primarily at antigenic sites, contribute to the antigenic properties observed over the evolution of GII.4 variants.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Virology
Jamie A. Kelly, Michael T. Woodside, Jonathan D. Dinman
Summary: Human population growth, climate change, and globalization are fueling the emergence of novel pathogenic viruses, posing serious threats to humanity. Research into -1 ribosomal frameshift in coronaviruses has revealed its virological importance and therapeutic potential.
Article
Virology
Bibha Dahal, Caitlin W. Lehman, Ivan Akhrymuk, Nicole R. Bracci, Lauren Panny, Michael D. Barrera, Nishank Bhalla, Jonathan L. Jacobs, Jonathan D. Dinman, Kylene Kehn-Hall
Summary: The research revealed that the loss of PERK significantly reduced VEEV and EEEV infectious titers in human primary astrocytes, pericytes, and endothelial cells. Moreover, PERK depletion also affected nonstructural protein translation and RNA production of various RNA viruses, suggesting that PERK is a potential target for antiviral drug development.
Article
Biochemistry & Molecular Biology
Mustapha Dahmani, Jack H. Cook, Jinyi C. Zhu, Sean P. Riley
Summary: Pathogenic Rickettsia are intracellular bacteria that cause life-threatening infectious diseases. The complement system plays a crucial role in combating Rickettsia infections, with the classical complement pathway being highlighted as essential for immune response.
MOLECULAR MICROBIOLOGY
(2021)
Article
Virology
Sneha Munshi, Krishna Neupane, Sandaru M. Ileperuma, Matthew T. J. Halma, Jamie A. Kelly, Clarissa F. Halpern, Jonathan D. Dinman, Sarah Loerch, Michael T. Woodside
Summary: Recurrent outbreaks of novel zoonotic coronavirus diseases in recent years have emphasized the importance of developing therapeutics with broad-spectrum activity against coronaviruses. Researchers explored whether small-molecule inhibitors of -1 programmed ribosomal frameshifting in SARS-CoV-2 also inhibited this process in a range of bat coronaviruses. The results showed that some drugs had strong activity against a broad spectrum of coronaviruses, establishing frameshift signals as a viable target for developing pan-coronaviral therapeutics.
Review
Virology
Joseph A. Kendra, Kentaro Tohma, Gabriel Parra
Summary: Noroviruses, with their extreme genetic diversity and rapid distribution, pose challenges for the development of effective vaccines and treatments. A comprehensive analysis of over 30,000 norovirus sequences from 1995 to 2019 revealed the predominance of the GII.4 genotype, along with the identification of numerous recombinant strains. This analysis provides a crucial historical foundation for future research on norovirus emergence, distribution, and the design of cross-protective vaccines.
REVIEWS IN MEDICAL VIROLOGY
(2022)
Article
Virology
Caitlin W. Lehman, Amy Smith, Jamie Kelly, Jonathan L. Jacobs, Jonathan D. Dinman, Kylene Kehn-Hall
Summary: EGR1 is a transcription factor associated with human astrocytoma cell infection by Venezuelan equine encephalitis virus (VEEV) and can regulate the expression of multiple inflammatory genes. EGR1 is upregulated in various alphavirus infections and plays an important role in cell death and inflammatory response following infection.
Article
Cell Biology
Kentaro Tohma, Lauren A. Ford-Siltz, Joseph A. Kendra, Gabriel Parra
Summary: RNA viruses have the ability to mutate and evade immunity. Antibody responses play a crucial role in viral immunity, but antigenic sites are subject to strong diversifying pressure. Using norovirus as a model, this study investigates the mechanisms of antigenic diversification in non-enveloped, rapidly evolving RNA viruses. The findings reveal that single neutralizing monoclonal antibodies (mAbs) target multiple antigenic sites of GII.4 norovirus. Interactions between multiple epitopes on the viral capsid surface result in a wide range of mAb-binding profiles and differences in immunodominance hierarchy between distantly related GII.4 variants. Time-ordered mutant viruses demonstrate a progressive change in antibody immunodominance along with point mutations during norovirus evolution. Thus, in addition to point mutations, switches in immunodominance could contribute to immune escape in RNA viruses.
Article
Immunology
Lauren A. A. Ford-Siltz, Kentaro Tohma, Gabriela S. S. Alvarado, Joseph A. A. Kendra, Kelsey A. A. Pilewski, James E. E. Crowe, Gabriel I. I. Parra
Summary: This study characterized a panel of human monoclonal antibodies that showed carbohydrate blocking activity against the current pandemic variant of norovirus. These antibodies demonstrated potent neutralization against the virus and exhibited differential binding patterns against major and minor variants. Mapping the antibodies to specific antigenic sites on the viral protein provided new insights into the development of cross-protective vaccines and therapeutics.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Virology
Gabriel I. Parra, Kentaro Tohma, Lauren A. Ford-Siltz, Patricia Eguino, Joseph A. Kendra, Kelsey A. Pilewski, Yamei Gao
Summary: Norovirus is a major human pathogen that can cause severe gastroenteritis. The diverse genotypes and antigenic variants of GII.4 noroviruses present challenges in vaccine development. This study analyzed the genetic changes in GII.4 Sydney_2012 viruses and found minimal antigenic diversification, providing insights for vaccine design.
JOURNAL OF VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lewis Rolband, Damian Beasock, Yang Wang, Yao-Gen Shu, Jonathan D. Dinman, Tamar Schlick, Yaoqi Zhou, Jeffrey S. Kieft, Shi-Jie Chen, Giovanni Bussi, Abdelghani Oukhaled, Xingfa Gao, Petr Sulc, Daniel Binzel, Abhjeet S. Bhullar, Chenxi Liang, Peixuan Guo, Kirill A. Afonin
Summary: The International Society of RNA Nanotechnology and Nanomedicine (ISRNN) aims to advance the development of functional nucleic acids and related nanotechnology platforms. This article summarizes recent advancements in viral biology, structure-function relationships of genomic viral RNA, and various applications in drug delivery and nanotechnology.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)