Article
Multidisciplinary Sciences
Robert M. Cox, Josef D. Wolf, Carolin M. Lieber, Julien Sourimant, Michelle J. Lin, Darius Babusis, Venice DuPont, Julie Chan, Kim T. Barrett, Diane Lye, Rao Kalla, Kwon Chun, Richard L. Mackman, Chengjin Ye, Tomas Cihlar, Luis Martinez-Sobrido, Alexander L. Greninger, John P. Bilello, Richard K. Plemper
Summary: Remdesivir is an antiviral drug approved for COVID-19 treatment, but its intravenous administration limits wider use. A study has shown that GS-621763, an oral prodrug of remdesivir parent nucleoside GS-441524, has good oral bioavailability and inhibits SARS-CoV-2 and variants of concern in ferrets, demonstrating therapeutic efficacy in a relevant animal model of SARS-CoV-2 infection.
NATURE COMMUNICATIONS
(2021)
Review
Pharmacology & Pharmacy
Dinesh S. Moirangthem, Laishram Surbala
Summary: COVID-19, caused by SARS-CoV-2, has led to a global pandemic. Remdesivir, a potential antiviral drug undergoing clinical trials, has shown promise in treating severe cases of the disease.
CURRENT DRUG TARGETS
(2021)
Article
Chemistry, Organic
Yuanchao Xie, Tianwen Hu, Yan Zhang, Daibao Wei, Wei Zheng, Fuqiang Zhu, Guanghui Tian, Haji A. Aisa, Jingshan Shen
Summary: This study presents a high-yield synthesis approach for preparing the key intermediate of remdesivir, which eliminates overaddition side reactions and enables scalable production.(KeyCode: BF3NITE)
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Cell Biology
Meghan S. Vermillion, Eisuke Murakami, Bin Ma, Jared Pitts, Adrian Tomkinson, Davin Rautiola, Darius Babusis, Hammad Irshad, Dustin Seigel, Cynthia Kim, Xiaofeng Zhao, Congrong Niu, Jesse Yang, Andrew Gigliotti, Nani Kadrichu, John P. Bilello, Scott Ellis, Roy Bannister, Raju Subramanian, Bill Smith, Richard L. Mackman, William A. Lee, Philip J. Kuehl, Jim Hartke, Tomas Cihlar, Danielle P. Porter
Summary: The pharmacokinetics and efficacy of inhaled Remdesivir (RDV) were investigated in African green monkeys (AGM). Inhalation RDV dosing produced comparable concentrations of the active triphosphate in lower respiratory tract tissues compared to intravenous RDV dosing but resulted in lower systemic exposures. An efficacy study in AGM showed reductions in viral replication in respiratory tract tissues with inhaled RDV dosing, which was similar to intravenous RDV dosing.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Kaxi Yu, Shuai Chen, Chander Amgoth, Guping Tang, Hongzhen Bai, Xiurong Hu
Summary: Two polymorphic phases of the antiviral drug remdesivir, RDV-I and RDV-II, were prepared and characterized using single-crystal X-ray diffraction, showing different packing patterns in their crystals. Their distinct pharmacokinetics, as revealed by in vitro and in vivo studies, underscore the significance of remdesivir drug formulations on patient outcomes when combating Covid-19.
Article
Chemistry, Medicinal
Richard L. Mackman, Rao V. Kalla, Darius Babusis, Jared Pitts, Kimberly T. Barrett, Kwon Chun, Venice Du Pont, Lauren Rodriguez, Jasmine Moshiri, Yili Xu, Michael Lee, Gary Lee, Blake Bleier, Anh-Quan Nguyen, B. Michael O'Keefe, Andrea Ambrosi, Meredith Cook, Joy Yu, Kassibla Elodie Dempah, Elaine Bunyan, Nicholas C. Riola, Xianghan Lu, Renmeng Liu, Ashley Davie, Tien-Ying Hsiang, Justin Dearing, Meghan Vermillion, Michael Gale Jr, Anita Niedziela-Majka, Joy Y. Feng, Charlotte Hedskog, John P. Bilello, Raju Subramanian, Tomas Cihlar
Summary: A prodrug called GS-5245 (Obeldesivir) has been discovered, which has low cytotoxicity and 3-7 times improved oral delivery of nucleoside GS-441524. It effectively inhibits SARS-CoV-2 replication and transcription, making it a promising treatment for COVID-19.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Virology
Thu Phan, Elizabeth J. Fay, Zion Lee, Stephanie Aron, Wei-Shou Hu, Ryan A. Langlois
Summary: The study introduces a new method InVERT, capable of quantifying all three RNA species produced by Influenza A virus, revealing the replication kinetics of different viral genome segments. The research further supports the complex regulation of RNA synthesis during replication, advancing our understanding of Influenza A virus replication dynamics.
JOURNAL OF VIROLOGY
(2021)
Article
Chemistry, Organic
Veeranjaneyulu Gannedi, Bharath Kumar Villuri, Sivakumar N. Reddy, Chiao-Chu Ku, Chi-Huey Wong, Shang-Cheng Hung
Summary: Remdesivir, developed by Gilead Sciences, is a promising treatment for COVID-19, although its synthesis has been challenging. A new one-pot synthesis method has been successfully developed to improve yield and purity, providing a potential pathway for industrial production.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Rita Humeniuk, Kavita Juneja, Shuguang Chen, Scott Ellis, Olena Anoshchenko, Deqing Xiao, Aaron Share, Matthew Johnston, Santosh Davies, Adam Dezure, Joe Llewellyn, Anu Osinusi, Helen Winter, Sandhya Girish, Ramesh Palaparthy, Mark Dresser
Summary: This study evaluated the pharmacokinetics and safety of inhaled remdesivir in healthy adults. The results showed that inhaled remdesivir exhibited linear and dose-proportional plasma distribution and different plasma concentrations when administered with a mouthpiece versus a sealed facemask. The evaluation of this administration route demonstrated that inhaled remdesivir was generally safe and well-tolerated.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Review
Chemistry, Multidisciplinary
Didier F. Vargas, Enrique L. Larghi, Teodoro S. Kaufman
Summary: The passage discusses the repositioning of the broad-spectrum antiviral Remdesivir and its main synthetic strategies, as well as recent progress and proposed improvements in the field. It provides a comprehensive view of the current state-of-the-art and important advances in the synthesis of Remdesivir.
Article
Pharmacology & Pharmacy
Lin Xu, Bo Tan, Di Huang, Meijie Yuan, Tingting Li, Ming Wu, Chaoyang Ye
Summary: The study found that remdesivir can inhibit renal fibrosis and alter the expression of Smad3 and Smad7 to exert its effects in obstructed kidneys.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemical Research Methods
Deqing Xiao, Kah Hiing John Ling, Thomas Tarnowski, Rita Humeniuk, Polina German, Anita Mathias, Jasper Chu, Yuan-Shek Chen, Eric van Ingen
Summary: This study validated LC-MS/MS methods for the determination of three analytes in human plasma, overcoming instability issues through diluted formic acid treatment and separate injections. The method demonstrated high precision and accuracy, with successful application in COVID-19 related clinical studies.
ANALYTICAL BIOCHEMISTRY
(2021)
Article
Chemistry, Medicinal
Hongxiang Hu, Mohamed Dit Mady Traore, Ruiting Li, Hebao Yuan, Miao He, Bo Wen, Wei Gao, Colleen B. Jonsson, Elizabeth A. Fitzpatrick, Duxin Sun
Summary: COVID-19 patients with severe symptoms lack effective antiviral treatment options. In this study, a new compound called MMT5-14 showed higher antiviral activity compared to remdesivir, the FDA-approved drug for those patients. MMT5-14 increased the concentration of the drug in the plasma and lungs, enhanced the accumulation of active metabolites in the lungs, and improved uptake and activation in lung epithelial cells. These findings suggest that MMT5-14 could be a potential antiviral drug for severe COVID-19 patients.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Hongming Zhang, Jibei Chen, Xiyong Wang, Baoan Chen
Summary: Remdesivir, a broad-spectrum antiviral agent, has garnered attention for its potential in treating COVID-19 amid the global spread of the virus. Despite promising signs of its efficacy from preclinical and clinical studies, more data is still needed to fully evaluate its effectiveness in treating COVID-19.
DISCOVERY MEDICINE
(2021)
Article
Immunology
Mei-Yi Lu, Ya-Lin Lin, Yali Kuo, Chi-Fen Chuang, Jen-Ren Wang, Fang Liao
Summary: EV71 infection in mice leads to limb paralysis, myositis, muscle calcification, and motor end plate defects. The presence of inflammatory and restorative macrophages at different stages of infection is associated with severe inflammation and recovery, respectively.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Chuangtao Ye, Dan Wang, He Liu, Hongwei Ma, Yangchao Dong, Min Yao, Yuan Wang, Hui Zhang, Liang Zhang, Linfeng Cheng, Zhikai Xu, Yingfeng Lei, Fanglin Zhang, Wei Ye
FRONTIERS IN PHARMACOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Min Yao, Yangchao Dong, Yuan Wang, He Liu, Hongwei Ma, Hui Zhang, Liang Zhang, Linfeng Cheng, Xin Lv, Zhikai Xu, Fanglin Zhang, Yingfeng Lei, Wei Ye
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2020)
Article
Pharmacology & Pharmacy
Yang Liu, Baozeng Sun, Jingyu Pan, Yuancai Feng, Wei Ye, Jiahao Xu, Mingfu Lan, Hao Sun, Xiyang Zhang, Yuanjie Sun, Shuya Yang, Jingqi Shi, Fanglin Zhang, Linfeng Cheng, Dongbo Jiang, Kun Yang
Summary: An EBOV GP recombinant DNA vaccine targeting MHC class II compartment was developed to enhance immune responses against Ebola virus. Mice immunized with this vaccine showed significantly higher serum antibody titers and neutralizing activity compared to other groups, along with antigen-specific T cells demonstrating high affinity for dominant peptides. Preliminary safety observation indicated no histological alterations, suggesting promise for the DNA vaccine candidate in combating Ebola epidemic.
ANTIVIRAL RESEARCH
(2021)
Letter
Infectious Diseases
Wei Ye, Yuan Wang, Yingfeng Lei, Fanglin Zhang
Article
Microbiology
Yongheng Yang, Mengyun Li, Yongtao Ma, Wei Ye, Yue Si, Xuyang Zheng, He Liu, Linfeng Cheng, Liang Zhang, Hui Zhang, Xijing Zhang, Yingfeng Lei, Lixin Shen, Fanglin Zhang, Hongwei Ma
Summary: This study found that there is differential expression of the lncRNA NEAT1-2 in the early stage of HTNV infection, and revealed the relationship between NEAT1-2 and macrophage activation and HTNV propagation. The study also identified the SREBP2 factor associated with macrophage activation, and found that NEAT1-2 can regulate the activity of SREBP2 to limit viral replication. In addition, the study found a negative correlation between the expression level of NEAT1-2 and viral load and the severity of HFRS.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Bin Wang, Jiawei Pei, Hui Zhang, Jia Li, Yamei Dang, He Liu, Yuan Wang, Liang Zhang, Libin Qi, Yuewu Yang, Linfeng Cheng, Yangchao Dong, Airong Qian, Zhikai Xu, Yingfeng Lei, Fanglin Zhang, Wei Ye
Summary: In this study, benidipine hydrochloride and other calcium channel blockers were found to inhibit the entry of hantaviruses, indicating the potential for repurposing FDA-approved drugs for the treatment of hantavirus infection.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Yajing Zhao, Ningbo Zhao, Yanxing Cai, Hui Zhang, Jia Li, Jiaqi Liu, Chuantao Ye, Yuan Wang, Yamei Dang, Wanying Li, He Liu, Lianqing Zhang, Yuexiang Li, Liang Zhang, Linfeng Cheng, Yangchao Dong, Zhikai Xu, Yingfeng Lei, Lu Lu, Yingjuan Wang, Wei Ye, Fanglin Zhang
Summary: The study discovered that griffithsin can effectively inhibit the growth and spread of Hantaan virus. In vitro experiments demonstrate that griffithsin can prevent the entry of the virus into host cells, and in vivo experiments showed partial protection of mice from Hantaan virus-induced death.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Yong-Liang Hu, Lian-Qing Zhang, Xiao-Qian Liu, Wei Ye, Yue-Xi Zhao, Liang Zhang, Zun-Xian Qiang, Lin-Xuan Zhang, Ying-Feng Lei, Dong-Bo Jiang, Lin-Feng Cheng, Fang-Lin Zhang
Summary: Three DNA vaccines encoding different proteins of CCHFV were evaluated, and the pVAX-LAMP1-CCHFV-NP vaccine showed the most effective protection against CCHFV infection in a human MHC transgenic mouse model. The pVAX-LAMP1-CCHFV-Gc vaccine also provided certain protection, but not as effective as pVAX-LAMP1-CCHFV-NP. The pVAX-LAMP1-CCHFV-Gn vaccine could not provide sufficient protection.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Editorial Material
Immunology
Wei Ye, Chuantao Ye, Jia Li, Yingfeng Lei, Fanglin Zhang
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jiawei Pei, Ye Tian, Wei Ye, Jiangfan Han, Yamei Dang, Tong Cheng, Wei Wang, Yipu Zhao, Weiliang Ye, Shuyuan Huangfu, Yu Li, Fanglin Zhang, Yingfeng Lei, Airong Qian
Summary: This study developed a novel antiviral therapeutic strategy against Varicella Zoster Virus (VZV) using RNA interference (RNAi), targeting the ORF7 gene. The recombinant ORF7-siRNA was effective in inhibiting VZV infection in vitro, and nano-liposomes were successfully used to deliver the siRNA to human skin models, maintaining normal skin morphology. Transdermal administration of the antiviral siRNA showed promise as a therapeutic strategy for the functional cure of VZV infection.
CELL AND BIOSCIENCE
(2023)
Article
Virology
Kerong Wang, Jian Zhang, Yongheng Yang, Yue Si, Ziqing Zhou, Xudong Zhu, Sushan Wu, He Liu, Hui Zhang, Liang Zhang, Linfeng Cheng, Wei Ye, Xin Lv, Yingfeng Lei, Xijing Zhang, Shilin Cheng, Lixin Shen, Fanglin Zhang, Hongwei Ma
Summary: The research revealed that STING enhances the host's immune response against hantavirus infection by triggering cellular autophagy, independent of IFN signaling. In mice experiments, administration of plasmids expressing mutant C-terminal tail STING protected the mice from lethal hantavirus infection. This study provides a novel antiviral pathway through the RIG-I-STING-autophagy pathway and offers new therapeutic strategies against hantavirus infection.
Article
Virology
Yue Si, Haijun Zhang, Ziqing Zhou, Xudong Zhu, Yongheng Yang, He Liu, Liang Zhang, Linfeng Cheng, Kerong Wang, Wei Ye, Xin Lv, Xijing Zhang, Wugang Hou, Gang Zhao, Yingfeng Lei, Fanglin Zhang, Hongwei Ma
Summary: This study reveals a novel immune evasion strategy used by Hantaan virus (HTNV), where HTNV activates receptor-interacting protein kinase 3 (RIPK3) to inhibit the interferon response and facilitate its replication. RIPK3 binds to STAT1 and inhibits STAT1 phosphorylation, thereby interfering with interferon-mediated antiviral activity.
Article
Virology
Wei Ye, Chuantao Ye, Yongliang Hu, Yangchao Dong, Yingfeng Lei, Fanglin Zhang
Article
Virology
Xue Wang, Cuixia Hu, Wei Ye, Jia Wang, Xiaofei Dong, Jie Xu, Xiaorong Li, Manfeng Zhang, Hongyun Lu, Fanglin Zhang, Wei Wu, Shaodong Dai, Hong-Wei Wang, Zhongzhou Chen
Summary: Rift Valley fever virus (RVFV) is a mosquito-borne virus that causes severe diseases in both humans and livestock. The RNA-dependent RNA polymerase (RdRp) encoded by the L segment of RVFV is essential for viral replication and transcription, and has multiple drug targets. In this study, the structure of RVFV L protein was determined, revealing its distinct priming loop and its role in RNA synthesis initiation.
JOURNAL OF VIROLOGY
(2022)
