Article
Chemistry, Medicinal
Mengjun Zheng, Wei Cong, Haoran Peng, Jie Qing, Huaxing Shen, Yaxin Tang, Chenchen Geng, Si Chen, Yan Zou, Wei-Dong Zhang, Hong-Gang Hu, Xiang Li
Summary: The pandemic caused by the highly pathogenic SARS-CoV-2 in 2019 has posed serious threats to human public safety. Research on designed stapled peptides has shown potential inhibitory effects, suggesting their use as effective drugs for treating and preventing the novel coronavirus.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Virology
Xinying Wang, Marli Vlok, Stephane Flibotte, Eric Jan
Summary: The study explores a novel viral translational mechanism, uncovering the IGR IRES sequence from ancient Northwest territories cripavirus dating back 700 years. The research demonstrates that aNCV IRES can bind to ribosomes and drive translation, supporting the historical significance of this viral translational mechanism.
Article
Medicine, Research & Experimental
Wan-Ling Wu, Chen-Yi Chiang, Szu-Chia Lai, Chia-Yi Yu, Yu-Ling Huang, Hung-Chun Liao, Ching-Len Liao, Hsin-Wei Chen, Shih-Jen Liu
Summary: Most therapeutic monoclonal antibodies (mAbs) target the receptor-binding domain (RBD) of SARS-CoV-2 spike protein, which is prone to mutations in variants. However, we identified mAbs that recognize the non-mutated S2 region of the spike protein and can neutralize SARS-CoV-2 infection and protect animals. Humanization of variable region sequences led to the selection of a high-affinity humanized mAb, hMab5.17, which effectively neutralized both SARS-CoV-2 and its variants. This suggests that an mAb targeting the S2 region could serve as a potential universal therapeutic for COVID-19.
Article
Medicine, Research & Experimental
Hui Li, Yuhang Chen, Junshi Zhang, Yongquan Lin, Zhilong Yang, Juan Tan, Wentao Qiao
Summary: This study investigated the mechanism of upregulation of c-fos mRNA translation efficiency when cellular protein synthesis is shut off. The results showed that EV71 infection led to increased levels of c-Fos protein expression in rhabdomyosarcoma cells. Further analysis revealed the role of PCBP2 and La in regulating the IRES activity of c-fos, providing a novel target for gene translation regulation.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2021)
Article
Virology
Taizhen Liang, Shiqi Xiao, Ziyao Wu, Xi Lv, Sen Liu, Meilin Hu, Guojie Li, Peiwen Li, Xiancai Ma
Summary: In this study, phenothiazine derivatives were identified as potential therapeutic drugs for the treatment of SARS-CoV-2 and future emerging human coronaviruses. These derivatives showed strong inhibition against pseudotyped SARS-CoV-2 and distinct variants of concern, including the Delta and Omicron variants. Mechanistic studies suggested that phenothiazines target the spike protein of SARS-CoV-2 and prevent proteolytic cleavage, thereby inhibiting viral infection.
Article
Virology
Leandro Fernandez-Garcia, Jenniffer Angulo, Hade Ramos, Aldo Barrera, Karla Pino, Jorge Vera-Otarola, Marcelo Lopez-Lastra
Summary: The DENV IRES enables viral protein synthesis under conditions that suppress canonical translation initiation, with resistance to eIF4G cleavage and enhanced activity in HEK 293T cells expressing Human rhinovirus 2A protease. This study characterizes the mechanism dependent on an internal ribosome entry site (IRES) for DENV mRNA translation initiation both in vitro and in cells.
JOURNAL OF VIROLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Xinjie Chen, Chen Wang, Yuan Lu
Summary: Facing the development of mRNA technology in medicine and vaccines, circular mRNA (circmRNA) has gained traction as a promising alternative due to its circular secondary structure and higher stability. This study explores different strategies for circmRNA biosynthesis through ribozyme catalysis and enzymatic reactions. The chosen methods, T4 Rnl 2 and Td ribozyme, show significant differences in ligation efficiency, with T4 Rnl 2 resulting in an 86% higher expression level of circmRNA. The screening of IRES sequences reveals mud crab dicistrovirus IRES as a high-efficiency sequence for translation in mammalian cells. These findings hold promise for the industrial production of circmRNAs and the development of mRNA vaccines, expanding the potential applications of circmRNAs in biomedicine.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Immunology
Guan-Hong Wu, Kuo-Ming Lee, Chia-Yu Kao, Shin-Ru Shih
Summary: The role of the internal ribosome entry site (IRES) in determining the neurovirulence of enteroviruses EV-A71 and CV-A16 was characterized using an oral inoculation model. Replacing EV-A71 IRES with CV-A16 abolished neuropathological phenotypes, indicating that IRES determines the neurotropic potential of these viruses. Tissue-specific replication can be reflected in cell-based characterization.
MICROBES AND INFECTION
(2023)
Article
Pharmacology & Pharmacy
Dongrong Yi, Quanjie Li, Han Wang, Kai Lv, Ling Ma, Yujia Wang, Jing Wang, Yongxin Zhang, Mingliang Liu, Xiaoyu Li, Jianxun Qi, Yi Shi, George F. Gao, Shan Cen
Summary: Berbamine hydrochloride effectively inhibits the replication of Ebola virus by disrupting the fusion of viral and cellular membranes. Targeting the viral glyco-protein provides a potential strategy for developing anti-Ebola virus drugs, and the repurposing of berbamine hydrochloride holds great promise.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Biology
Yuxuan Zhou, Jingcheng Wu, Shihao Yao, Yulian Xu, Wenbin Zhao, Yunguang Tong, Zhan Zhou
Summary: In this study, we propose DeepCIP, a multimodal deep learning approach that uses both sequence and structural information to predict internal ribosome entry sites (IRESs) in circRNAs. Our results show that DeepCIP outperforms other methods in predicting circRNA IRESs. The analysis of the learned sequence patterns by DeepCIP aligns with previous discoveries of motifs facilitating circRNA translation. Therefore, DeepCIP has the potential to advance the study of circRNA coding potential and contribute to circRNA-based drug design.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Review
Virology
Brenda Lopez-Ulloa, Yazmin Fuentes, Magdalena S. Pizarro-Ortega, Marcelo Lopez-Lastra
Summary: In this review, we discuss vRNA IRES-mediated translation initiation, highlighting the role of RNA-binding proteins (RBPs), other than the canonical translation initiation factors, in regulating their activity.
Article
Plant Sciences
Fredy Brice Simo Nemg, Saikat De, Supriya Suman Keshry, Prabhudutta Mamidi, Frederic Nico Njayou, Maurice Demanou, Paul Moundipa Fewou, Soma Chattopadhyay
Summary: This study explores the anti-chikungunya activities of certain plant extracts in Cameroon, aiming to identify potential sources for the development of anti-CHIKV molecules in the future. Nine medicinal plants were identified through an ethnobotanical survey, with four extracts showing antiviral activity against CHIKV. Further studies revealed the mechanisms of action of these extracts in inhibiting various stages of viral infection.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Microbiology
Jibin Sadasivan, Marli Vlok, Xinying Wang, Arabinda Nayak, Raul Andino, Eric Jan
Summary: Viruses have evolved mechanisms to modulate cellular pathways to facilitate infection, such as inhibiting the formation of stress granules (SG). This study focuses on the 1A protein encoded by the Cricket paralysis virus (CrPV), which can block SG formation. The researchers found that the E3 ubiquitin-ligase binding domain and the R146 residue of CrPV-1A are necessary for SG inhibition. They also identified a host protein, Nup358/RanBP2, that is targeted and degraded in CrPV-infected cells in an R146-dependent manner, and the depletion of Nup358 blocks SG formation. This study reveals a novel viral strategy in modulating stress granule formation to promote virus infection.
Article
Multidisciplinary Sciences
Miwa Okamoto, Rika Kurino, Ryu Miura, Kenzo Takada
Summary: In this study, a fully human neutralizing monoclonal antibody EV2038 was found to effectively inhibit human cytomegalovirus infection and viral cell-to-cell spread. This antibody showed a strong inhibitory effect on various laboratory strains and clinical isolates, including ganciclovir-resistant isolates.
Review
Biochemistry & Molecular Biology
Rita Marques, Rafaela Lacerda, Luisa Romao
Summary: RNA-based therapies targeting IRESs and ITAFs have shown potential benefits in various conditions. IRES-mediated translation is an alternative mechanism that helps maintain protein synthesis and is involved in stress response and disease development. The relationship between IRESs, ITAFs, tumorigenesis, and therapy resistance has been studied, providing new therapeutic targets and approaches. In addition, dysregulation of IRES-dependent translation initiation is also associated with neurological and cardiovascular diseases, muscular atrophies, and other syndromes.
Article
Pharmacology & Pharmacy
Yuchen Nan, Zexu Ma, Harilakshmi Kannan, David A. Stein, Patrick I. Iversen, Xiang-Jin Meng, Yan-Jin Zhang
ANTIVIRAL RESEARCH
(2015)
Article
Medicine, General & Internal
Alison E. Heald, Jay S. Charleston, Patrick L. Iversen, Travis K. Warren, Jay B. Saoud, Mohamed Al-Ibrahim, Jay Wells, Kelly L. Warfield, Dana L. Swenson, Lisa S. Welch, Peter Sazani, Michael Wong, Diane Berry, Edward M. Kaye, Sina Bavari
NEW ENGLAND JOURNAL OF MEDICINE
(2015)
Article
Microbiology
Travis K. Warren, Chris A. Whitehouse, Jay Wells, Lisa Welch, Alison E. Heald, Jay S. Charleston, Pete Sazani, St Patrick Reid, Patrick L. Iversen, Sina Bavari
Article
Infectious Diseases
Travis K. Warren, Chris A. Whitehouse, Jay Wells, Lisa Welch, Jay S. Charleston, Alison Heald, Donald K. Nichols, Marc E. Mattix, Gustavo Palacios, Jeffrey R. Kugleman, Patrick L. Iversen, Sina Bavari
PLOS NEGLECTED TROPICAL DISEASES
(2016)
Article
Multidisciplinary Sciences
Yusuke Echigoya, Akinori Nakamura, Tetsuya Nagata, Nobuyuki Urasawa, Kenji Rowel Q. Lim, Nhu Trieu, Dharminder Panesar, Mutsuki Kuraoka, Hong M. Moulton, Takashi Saito, Yoshitsugu Aoki, Patrick Iversen, Peter Sazani, Ryszard Kole, Rika Maruyama, Terry Partridge, Shin'ichi Takeda, Toshifumi Yokota
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Article
Microbiology
Alison E. Heald, Patrick L. Iversen, Jay B. Saoud, Peter Sazani, Jay S. Charleston, Tim Axtelle, Michael Wong, William B. Smith, Apinya Vutikullird, Edward Kaye
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2014)
Article
Biotechnology & Applied Microbiology
Hossein Khiabanian, Zachary Carpenter, Jeffrey Kugelman, Joseph Chan, Vladimir Trifonov, Elyse Nagle, Travis Warren, Patrick Iversen, Sina Bavari, Gustavo Palacios, Raul Rabadan
Article
Immunology
Bruce L. Geller, Kimberly Marshall-Batty, Frederick J. Schnell, Mattie M. McKnight, Patrick L. Iversen, David E. Greenberg
JOURNAL OF INFECTIOUS DISEASES
(2013)
Article
Multidisciplinary Sciences
Sumit Punj, Prasad Kopparapu, Hyo Sang Jang, Jessica L. Phillips, Jamie Pennington, Diana Rohlman, Edmond O'Donnell, Patrick L. Iversen, Siva Kumar Kolluri, Nancy I. Kerkvliet
Article
Biochemistry & Molecular Biology
Rekha G. Panchal, Dan V. Mourich, Steven Bradfute, Laura L. Hauck, Kelly L. Warfield, Patrick L. Iversen, Sina Bavari
NUCLEIC ACID THERAPEUTICS
(2014)
Article
Biochemistry & Molecular Biology
Dan V. Mourich, Shannon K. Oda, Frederick J. Schnell, Stacy L. Crumley, Laura L. Hauck, Carla A. Moentenich, Nikki B. Marshall, Dave J. Hinrichs, Patrick L. Iversen
NUCLEIC ACID THERAPEUTICS
(2014)
Article
Pharmacology & Pharmacy
Andrew J. Annalora, Marija Jozic, Craig B. Marcus, Patrick L. Iversen
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2019)
Editorial Material
Infectious Diseases
Sina Bavari, Patrick L. Iversen
LANCET INFECTIOUS DISEASES
(2020)
Article
Pharmacology & Pharmacy
John H. Beigel, Jocelyn Voell, Paula Munoz, Parag Kumar, Kristina M. Brooks, Jianbo Zhang, Patrick Iversen, Alison Heald, Michael Wong, Richard T. Davey
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2018)
Review
Pharmacology & Pharmacy
Andrew J. Annalora, Craig B. Marcus, Patrick L. Iversen
DRUG METABOLISM AND DISPOSITION
(2017)