Article
Multidisciplinary Sciences
Yu Sun, Laura Abriola, Rachel O. Niederer, Savannah F. Pedersen, Mia M. Alfajaroe, Valter Silva Monteiro, Craig B. Wilen, Ya-Chi Ho, Wendy Gilbert, Yulia Surovtseva, Brett D. Lindenbach, Junjie U. Guo
Summary: The study found that merafloxacin can inhibit -1 PRF activity of SARS-CoV-2 and is similarly effective on other betacoronaviruses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Shuting Yan, Qiyao Zhu, Jenna Hohl, Alex Dong, Tamar Schlick
Summary: The frameshifting RNA element (FSE) in coronaviruses (CoVs) plays a crucial role in regulating the viral protein production and is considered as a potential drug candidate. By analyzing the conformational landscapes of FSEs with increasing sequence lengths, researchers have identified competing stems and topological changes that contribute to frameshifting efficiency. This study provides insights into the structural evolution of FSEs and the potential for therapeutic interventions against a broad spectrum of CoVs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
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.
Article
Biochemistry & Molecular Biology
Xiaolan Huang, Zhihua Du
Summary: Pseudoknots play important roles in RNA viruses, such as stimulating ribosomal frameshifting or stop codon readthrough. Recent studies have confirmed the significance of three-stemmed pseudoknots in SARS-CoV-2 and related coronaviruses. Additional complex pseudoknots with various structural elements have also been identified, expanding our understanding of their regulatory functions in different virus families.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Anna A. Mikkelsen, Feng Gao, Elizabeth Carino, Sayanta Bera, Anne E. Simon
Summary: Plus-strand RNA viruses often use -1 programmed ribosomal frameshifting to maximize their coding capacity. This study discovered six tertiary interactions associated with the FSE of citrus yellow vein associated virus, which covers three-quarters of the genomic RNA. Two long-distance interactions connect sequences on opposite sides of the critical FSE central stem, destabilizing the FSE and potentially allowing ribosome progression through a disrupted upstream FSE.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Tamar Schlick, Qiyao Zhu, Abhishek Dey, Swati Jain, Shuting Yan, Alain Laederach
Summary: The FSE of SARS-CoV-2 is a promising target for Covid-19 therapy, but its structures and mechanisms pose challenges. Research suggests that the FSE may adopt multiple conformations, including the 3-stem H-type and HL-type pseudoknots, as well as the unknotted 3-way junction RNA. These findings advance our understanding of the virus frameshifting process and lifecycle, indicating potential avenues for therapeutic intervention.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Virology
Bayleigh E. Benner, James W. Bruce, Jacob R. Kentala, Magdalena Murray, Jordan T. Becker, Pablo Garcia-Miranda, Paul Ahlquist, Samuel E. Butcher, Nathan M. Sherer
Summary: This study reveals the mechanisms of Gag-Pol protein incorporation into HIV-1 virions. The study found that GP is enriched in virions about 3-fold compared to cells, and viral infectivity is better maintained at subphysiological levels of GP. It was also discovered that GP is more efficiently incorporated into virions when synthesized from the same mRNA as Gag. Furthermore, virions exhibit a strong upper limit to trans-delivered GP incorporation. These results provide new insights into the importance and regulation of GP in HIV-1 virion assembly.
JOURNAL OF VIROLOGY
(2022)
Article
Pharmacology & Pharmacy
Carmine Varricchio, Gregory Mathez, Trestan Pillonel, Claire Bertelli, Laurent Kaiser, Caroline Tapparel, Andrea Brancale, Valeria Cagno
Summary: Aminoglycoside antibiotic gentamicin has been found to effectively combat various variants of SARS-CoV-2 in different cell lines and respiratory tissue models. It inhibits viral RNA replication and protein expression at an early stage by targeting the ribosomal frameshift signal of SARS-CoV-2.
ANTIVIRAL RESEARCH
(2022)
Review
Chemistry, Multidisciplinary
Viktoriya S. Anokhina, Benjamin L. Miller
Summary: Treating HIV-1 has moved from targeting viral enzymes to looking for new therapeutic targets, with -1 PRF gaining attention as a potential intervention point crucial for correct viral particle assembly. Despite being deleterious for the virus when dysregulated, -1 PRF is also exploited by other viruses like coronaviruses, including SARS-CoV-2, implying the importance of exploring similar strategies in antiviral development.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Virology
Du Yu, Yundi Zhao, Junhui Pan, Xingmiao Yang, Zhenjie Liang, Shengda Xie, Ruibing Cao
Summary: C19orf66, a novel interferon-stimulated gene product, can inhibit JEV replication by targeting -1 PRF and the NS3 protein. The study suggests that C19orf66 may possess at least two different mechanisms of antagonizing JEV infection.
Article
Multidisciplinary Sciences
Howard Gamper, Haixing Li, Isao Masuda, D. Miklos Robkis, Thomas Christian, Adam B. Conn, Gregor Blaha, E. James Petersson, Ruben L. Gonzalez, Ya-Ming Hou
Summary: The study investigates the translation of quadruplet codons by a +1-frameshifting tRNA SufB2, revealing that SufB2 initially uses triplet anticodon-codon pairing in the 0-frame to decode the quadruplet codon before shifting to the +1-frame during tRNA-mRNA translocation. The frameshifting mechanism of SufB2 involves perturbation of a crucial ribosome conformational change, highlighting the potential for engineering specific ribosome conformational changes to enhance genome recoding efficiency.
NATURE COMMUNICATIONS
(2021)
Article
Virology
Dae-Gyun Ahn, Gun Young Yoon, Sunhee Lee, Keun Bon Ku, Chonsaeng Kim, Kyun-Do Kim, Young-Chan Kwon, Geon-Woo Kim, Bum-Tae Kim, Seong-Jun Kim
Summary: Recent outbreaks of zoonotic coronaviruses, such as MERS-CoV and SARS-CoV-2, have caused significant casualties and economic shock. A novel compound, KCB261770, has been identified to effectively inhibit MERS-CoV frameshifting, showing potential as a drug candidate for interfering with pan-coronavirus frameshifting.
Article
Biochemical Research Methods
Sara Ibrahim Omar, Meng Zhao, Rohith Vedhthaanth Sekar, Sahar Arbabi Moghadam, Jack A. Tuszynski, Michael T. Woodside
Summary: The coronavirus responsible for COVID-19 controls viral protein production through a unique RNA pseudoknot structure, which may be a potential target for treating the disease. Computational modeling revealed multiple possible conformations of the SARS-CoV-2 pseudoknot, providing insight for future experiments and drug discovery efforts. The study also identified unusual structures involving RNA threading through helical junctions, which could aid in understanding and developing treatments for SARS-CoV-2.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Gabriel Demo, Howard B. Gamper, Anna B. Loveland, Isao Masuda, Christine E. Carbone, Egor Svidritskiy, Ya-Ming Hou, Andrei A. Korostelev
Summary: The study found that the ribosome and EF-G cooperate to induce +1 frameshifting during tRNA-mRNA translocation.
NATURE COMMUNICATIONS
(2021)
Article
Biochemical Research Methods
Luke Trinity, Ian Wark, Lance Lansing, Hosna Jabbari, Ulrike Stege
Summary: Identifying inter-viral structural similarity in frameshifting pseudoknots is valuable for treatment development. We developed Shapify algorithm for improved prediction of possibly pseudoknotted RNA secondary structures. Our study sheds light on the structure formation of the SARS-CoV-2 and MERS-CoV frameshifting pseudoknots.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Marco Lezzerini, Marianna Penzo, Marie-Francoise O'donohue, Carolina Marques dos Santos Vieira, Manon Saby, Hyung L. Elfrink, Illja J. Diets, Anne-Marie Hesse, Yohann Coute, Marc Gastou, Alexandra Nin-Velez, Peter G. J. Nikkels, Alexandra N. Olson, Evelien Zonneveld-Huijssoon, Marjolijn C. J. Jongmans, GuangJun Zhang, Michel van Weeghel, Riekelt H. Houtkooper, Marcin W. Wlodarski, Roland P. Kuiper, Marc B. Bierings, Jutte van der Werff ten Bosch, Thierry Leblanc, Lorenzo Montanaro, Jonathan D. Dinman, Lydie Da Costa, Pierre-Emmanuel Gleizes, Alyson W. MacInnes
NUCLEIC ACIDS RESEARCH
(2020)
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
Editorial Material
Biochemistry & Molecular Biology
Alexandra N. Olson, Jonathan D. Dinman
Article
Biochemistry & Molecular Biology
Maria J. Nabais Sa, Alexandra N. Olson, Grace Yoon, Graeme A. M. Nimmo, Christopher M. Gomez, Michel A. Willemsen, Francisca Millan, Alexandra Schneider, Rolph Pfundt, Arjan P. M. de Brouwer, Jonathan D. Dinman, Bert B. A. de Vries
HUMAN MOLECULAR GENETICS
(2020)
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
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.
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
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)