Article
Microbiology
Hye-Jin Shin, Mi-Hwa Kim, Joo-Youn Lee, Insu Hwang, Gun-Young Yoon, Hae-Soo Kim, Young-Chan Kwon, Dae-Gyun Ahn, Kyun-Do Kim, Bum-Tae Kim, Seong-Jun Kim, Chonsaeng Kim
Summary: The Zika virus and dengue virus are closely related and may exacerbate disease when circulating together. A potential drug has been discovered to effectively inhibit the infection of both viruses, showing promise for the development of more potent antiviral drugs.
Article
Biophysics
Wen Hao Kenneth Lee, Wei Liu, Jing-Song Fan, Daiwen Yang
Summary: The study revealed the dynamic equilibrium between closed and open conformations of the NS3 protease-NS2B complex of dengue virus in aqueous solution. The stability of NS2B was found to affect the equilibrium between closed and open conformations, with the proteolytic activity of the complex correlating well with the closed conformation. These findings suggest that the closed-open conformational equilibrium can be utilized to control the replication of dengue virus by both nature and human intervention.
BIOPHYSICAL JOURNAL
(2021)
Article
Multidisciplinary Sciences
Omar Cruz-Arreola, Abdu Orduna-Diaz, Fabiola Dominguez, Julio Reyes-Leyva, Veronica Vallejo-Ruiz, Lenin Dominguez-Ramirez, Gerardo Santos-Lopez
Summary: This study explored the potential targets for treating dengue and Zika viruses by analyzing the binding affinity of certain molecules found in medicinal plants to NS3-helicase and NS3-protease. The results suggest that quercetin derivatives could block the activity of NS3-protease in both viruses. A new molecule called MOD10 was designed and showed improved interaction and trajectory compared to the original molecules. These findings provide new insights for the development of antiviral treatments against dengue and Zika viruses.
Article
Biochemistry & Molecular Biology
Agnieszka Dabrowska, Aleksandra Milewska, Joanna Ner-Kluza, Piotr Suder, Krzysztof Pyrc
Summary: Mass spectrometry is a powerful tool in proteomics analysis, capable of detecting hundreds of proteins, but may lead to confusing results and the biological relevance of detected targets cannot always be confirmed. Deep recognition of the biological role of proteins in virus infection processes is essential for a complete understanding.
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
Biochemistry & Molecular Biology
Fadi G. Saqallah, Manal A. Abbas, Habibah A. Wahab
Summary: Dengue virus is a mosquito-borne virus that can cause various complications. A tetravalent vaccine is available for children, and the NS2b/NS3 protease is a key target for antiviral agents. Natural products have shown potential as inhibitors of dengue virus, with some compounds found to inhibit the NS2b/NS3 protease. However, further in vivo and clinical studies are needed.
Article
Biochemistry & Molecular Biology
Tanaya Bagga, Nikhil Kumar Tulsian, Yu Keung Mok, R. Manjunatha Kini, J. Sivaraman
Summary: This study reveals the interaction and ubiquitination process between TRIM69 and Dengue NS2B-NS3 Delta pro, and identifies the conservation of TRIM69 targeting regions across various flaviviruses.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Zafirah Liyana Abdullah, Hui-Yee Chee, Rohana Yusof, Fazlin Mohd Fauzi
Summary: This study aimed to repurpose old drugs as novel DENV NS3 inhibitors. Predictive models were built using bioactivity data to screen for potential NS3 inhibitors. In vitro validation showed moderate inhibitory effects of selected drugs and proposed compounds against DENV.
Article
Chemistry, Medicinal
Shenyou Nie, Jidong Zhao, Xiaowei Wu, Yuan Yao, Fangrui Wu, Yi-Lun Lin, Xin Li, Alexander R. Kneubehl, Megan B. Vogt, Rebecca Rico-Hesse, Yongcheng Song
Summary: A novel series of compounds have been discovered as potent inhibitors of the Zika virus protease, with the most effective ones also showing inhibitory effects on dengue and West Nile virus. The most potent compounds were able to strongly inhibit Zika virus replication in cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Virology
Tadahisa Teramoto
Summary: Enzyme activities for replicating DENV 5' cap positive (+) sense RNA have been shown to reside in NS3 and NS5. However, it remains unknown how these enzymes coordinately synthesize negative (-) sense RNA, from which abundant 5' cap (+) sense RNA is produced. We previously revealed that NS5 dimerization and NS5 methyltransferase(MT)-NS3HEL interaction are important for DENV replication. Here, we found that replication incompetence due to NS3PRO or HEL replacement was compensated by a mutation at HEL or NS2B, respectively, suggesting that the interactions among NS2B, NS3PRO, and HEL are critical for DENV replication.
JOURNAL OF VIROLOGY
(2023)
Article
Chemistry, Medicinal
Thales Kronenberger, Mateus Sa Magalhaes Serafim, Arun Kumar Tonduru, Vinicius Goncalves Maltarollo, Antti Poso
Summary: Dengue is a tropical disease caused by the dengue virus, with an estimated 300 million new cases each year. Due to limited vaccine efficacy and lack of effective antiviral treatment, new drug candidates are urgently needed. Molecular dynamics simulations were conducted to study the conformational changes in the DENV-3 NS3-NS2B complex, revealing multiple druggable subpockets that can be explored in drug discovery efforts.
Article
Pharmacology & Pharmacy
Muhammad Usman Mirza, Ida Alanko, Michiel Vanmeert, Kendall M. Muzzarelli, Outi M. H. Salo-Ahen, Iskandar Abdullah, Iulia A. Kovari, Sandra Claes, Steven De Jonghe, Dominique Schols, Raymond F. Schinazi, Ladislau C. Kovari, John F. Trant, Sarfraz Ahmad, Matheus Froeyen
Summary: This study used a computer-aided structure-based approach to screen a library of compounds against ZIKV NS2B-NS3 protease. Several compounds showed promising activity against the protease, and one compound also exhibited anti-ZIKV activity in whole cells. This research provides a promising starting point for the development of novel compounds against ZIKV.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Biophysics
Skomantas Serapinas, Justina Gineityte, Marius Butkevicius, Rapolas Danilevicius, Marius Dagys, Dalius Ratautas
Summary: This paper presents a new bioelectronic device for the detection of nuclease activity in various fluids. The developed sensor enables rapid and sensitive determination of DNase activity, with high accuracy and reproducibility demonstrated in real human saliva samples. The technology has the potential to improve nuclease quality control processes in the pharmaceutical/biotechnology industry and provide new insights into the importance of nucleases for medical applications.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Immunology
Sheng-Hsuan Wang, Bai-Jiun Kuo, Tzu-Chuan Ho, Shu-Wen Wan, Ko-Lun Yen, Po-Hui Huang, Oscar Guey Chuen Perng, Po-Lin Chen, Yu-Wen Chien, Yu-Chih Lo
Summary: This study found that dengue patients have elevated levels of serum FLCs, which are associated with disease severity. The study suggests that λ-FLCs can serve as serum markers for identifying and classifying dengue disease. Additionally, the study reveals that the elevation of serum λ-FLCs is mediated through NS3 protease-mediated antibody cleavage.
Article
Chemistry, Medicinal
Lata R. Ganji, Lekha Gandhi, Venkataramana Musturi, Meena A. Kanyalkar
Summary: The study focuses on the threat of deaths or critical health issues caused by Dengue virus infection. A series of compounds targeting the dengue protease NS2B-NS3 was designed and synthesized, with CA2, BZ1, and BS2 showing more potent and efficacious protease inhibition activity compared to the standard quercetin.
MEDICINAL CHEMISTRY RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Jing-Xing Yang, Jen-Chih Tseng, Guann-Yi Yu, Yunping Luo, Chi-Ying F. Huang, Yi-Ren Hong, Tsung-Hsien Chuang
Summary: Vaccines are important for controlling microbial infections and preventing epidemic diseases. The development of adjuvants, specifically Toll-like receptor (TLR) agonists, has seen significant progress in recent years for human vaccines. The COVID-19 pandemic has also accelerated the clinical research of TLR agonist-based adjuvants. This paper reviews the agonists for TLR activation and their molecular mechanisms, with a focus on recent advances in TLR agonist-based vaccine adjuvants for infectious diseases.
Article
Biochemistry & Molecular Biology
Hung-Chun Liao, Wan-Ling Wu, Chen-Yi Chiang, Min-Syuan Huang, Kuan-Yin Shen, Yu-Ling Huang, Suh-Chin Wu, Ching-Len Liao, Hsin-Wei Chen, Shih-Jen Liu
Summary: During the COVID-19 pandemic, global mass vaccination is crucial for achieving herd immunity. The study shows that the S-Trimer vaccine, when adjuvanted with SWE, induces strong antibody and cellular immune responses, providing neutralizing antibodies against the original and variant strains of SARS-CoV-2. Additionally, the SWE adjuvant allows for a lower vaccine dosage while maintaining effectiveness.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Hong-Jyun Huang, Martyr Yang, Hsin-Wei Chen, Shuying Wang, Chih-Peng Chang, Tzong-Shiann Ho, Yu-San Kao, Sen-Mao Tien, Hsing-Han Lin, Po-Chun Chang, Yen-Chung Lai, Yu-Peng Hsiao, Yi-Ling Liu, Chiao-Hsuan Chao, Robert Anderson, Trai-Ming Yeh, Yee-Shin Lin, Shu-Wen Wan
Summary: This study developed a modified DENV vaccine candidate with enhanced features by combining modifications of two DENV proteins. The vaccine candidate showed protective effects against DENV infection in a mouse model, indicating its potential clinical application.
Article
Immunology
Jhe-Jhih Lin, Chih-Feng Tien, Yi-Ping Kuo, En-Ju Lin, Wei-Hsiang Tsai, Ming-Yu Chen, Pei-Ju Tsai, Yu-Wen Su, Nikhil Pathak, Jinn-Moon Yang, Chia-Yi Yu, Zih-Shiuan Chuang, Han-Chieh Wu, Wan-Ting Tsai, Shih-Syong Dai, Hung-Chun Liao, Kit Man Chai, Yu-Siang Su, Tsung-Hsien Chuang, Shih-Jen Liu, Hsin-Wei Chen, Horng-Yunn Dou, Feng-Jui Chen, Chiung-Tong Chen, Chin-Len Liao, Guann-Yi Yu
Summary: An effective COVID-19 vaccine against broad SARS-CoV-2 variants is still needed. This study used a vesicular stomatitis virus (VSV)-based vector to express the SARS-CoV-2 Spike protein for better vaccine designs. The recombinant VSV-spike virus with C-terminal 19 amino acid truncation (S Delta 19 Rep) induced protective immunity against SARS-CoV-2 infection in hamsters. Mutations blocking enzymatic processing of the Spike protein were identified and found to enhance immune responses. Vaccination with the mutated virus provided high antibody response and protection against a lethal SARS-CoV-2 challenge.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Tsai-Teng Tzeng, Kit Man Chai, Kuan-Yin Shen, Chia-Yi Yu, Shiu-Ju Yang, Wan-Chun Huang, Hung-Chun Liao, Fang-Feng Chiu, Horng-Yunn Dou, Ching-Len Liao, Hsin-Wei Chen, Shih-Jen Liu
Summary: This study reports an electroacupuncture machine-based method for DNA vaccine delivery of the COVID-19 DNA vaccine. The method was found to efficiently induce neutralizing antibodies and Th1-biased immune responses in mice and provide protection against SARS-CoV-2 challenge in hamsters. T-cell epitope mapping revealed specific regions of reactivity. The method was deemed safe based on preclinical toxicology studies, and the raised antisera showed cross-neutralization against different variants of concern.
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
Multidisciplinary Sciences
Chih-Feng Tien, Wan-Ting Tsai, Chun Hwa Chen, Hui-Ju Chou, Mingzi M. Zhang, Jhe-Jhih Lin, En-Ju Lin, Shih-Syong Dai, Yueh-Hsin Ping, Chia-Yi Yu, Yi-Ping Kuo, Wei-Hsiang Tsai, Hsin-Wei Chen, Guann-Yi Yu
Summary: Post-translational modifications play critical roles in protein folding, stability, trafficking, and function. This study investigates the impact of glycosylation and palmitoylation on the maturation and infectivity of SARS-CoV-2 spike protein. The results show that mutations in specific motifs alter intracellular trafficking, glycosylation pattern, and infectivity of pseudoviruses, highlighting the importance of these modifications in the fusion and infection mediated by the S protein.
Article
Virology
Kuan-Yin Shen, Chung-Hsiang Yang, Chiung-Tong Chen, Hui-Min Ho, Fang-Feng Chiu, Chiung-Yi Huang, Hung-Chun Liao, Chia-Wei Hsu, Guann-Yi Yu, Ching-Len Liao, Hsin-Wei Chen, Ming-Hsi Huang, Shih-Jen Liu
Summary: The major challenge in COVID-19 vaccine effectiveness is immune escape by SARS-CoV-2 variants. An Omicron-specific mRNA vaccine was designed to overcome this challenge. Animal studies showed that the vaccine generates non-neutralizing antibodies or cellular immunity that can recognize both Wuhan and Omicron variants, providing protection against Wuhan virus challenge.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Pharmacology & Pharmacy
Hui-Min Ho, Chiung-Yi Huang, Chung-Hsiang Yang, Shih-Jen Liu, Hsin-Wei Chen, Guann-Yi Yu, Jen-Kun Chen, Tsung-Hsien Chuang, Ming-Hsi Huang
Summary: Nasal spray vaccination is a promising strategy for inducing protection against respiratory SARS-CoV-2 coronavirus. This study demonstrates the potential of PELC:CpG as a mucosal adjuvant that enhances immune responses and cell-mediated immunity, which has implications for the development of a nasal spray vaccine against COVID-19.
Article
Immunology
Ming-Shu Hsieh, Mei-Yu Chen, Chia-Wei Hsu, Yu-Wen Tsai, Fang-Feng Chiu, Cheng-Lung Hsu, Chang-Ling Lin, Chiao-Chieh Wu, Ling-Ling Tu, Chen-Yi Chiang, Shih-Jen Liu, Ching-Len Liao, Hsin-Wei Chen
Summary: Formyl peptide receptor-like 1 inhibitor protein (FLIPr) is a potential vaccine candidate produced by Staphylococcus aureus for reducing its virulence and biofilm formation. Recombinant lipidated FLIPr (rLF) was produced to increase its immunogenicity and showed to elicit potent anti-FLIPr responses and overcome FLIPr-mediated inhibition of phagocytosis. Additionally, rLF acts as an effective adjuvant by inducing strong and long-lasting immune responses in mice, supporting its potential use to enhance vaccine efficacy and abolish FLIPr-mediated immunosuppressive effects.
Article
Virology
Hung-Chun Liao, Min-Syuan Huang, Fang-Feng Chiu, Kit Man Chai, Ching-Len Liao, Suh-Chin Wu, Hsin-Wei Chen, Shih-Jen Liu
Summary: This study reports a novel COVID-19 vaccine that combines recombinant S protein with a DNA vaccine. The combination vaccine induces strong T-cell immune response and enhances immune indicators such as antibody titers. In animal experiments, hamsters vaccinated with the combination vaccine showed no weight loss and had low viral load in the lungs, indicating the important role of this vaccine in disease control.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Medicine, General & Internal
Hsing-Han Li, Matthew P. Su, Shih-Cheng Wu, Hsiao-Hui Tsou, Meng-Chun Chang, Yu-Chieh Cheng, Kuen-Nan Tsai, Hsin-Wei Wang, Guan-Hua Chen, Cheng-Kang Tang, Pei -Jung Chung, Wan-Ting Tsai, Li-Rung Huang, Yueh Andrew Yueh, Hsin-Wei Chen, Chao-Ying Pan, Omar S. Akbari, Hsiao-Han Chang, Guann-Yi Yu, John M. Marshall, Chun-Hong Chen
Summary: A study using a mouse model revealed the potential of mechanical transmission of dengue virus, independent of viral replication in mosquitoes. This finding suggests the possibility of larger outbreaks and has implications for vector control strategies. It also raises the possibility of similar mechanical transmission routes in other disease-carrying mosquitoes.
Article
Cell Biology
Chen-Yi Chiang, Mei-Yu Chen, Chia-Wei Hsu, Chia-Yeh Liu, Yu-Wen Tsai, Hung-Chun Liao, Jia-Ying Yan, Zih-Shiuan Chuang, Hsin- Wang, Chien-Hsiung Pan, Chia-Yi Yu, Guann-Yi Yu, Ching-Len Liao, Shih-Jen Liu, Hsin-Wei Chen
Summary: This study generated high-quality monoclonal antibodies using a DNA prime-protein boost approach and found that one antibody displayed the best potency in terms of binding affinity and neutralizing capacity. This antibody was able to protect animals from SARS-CoV-2 infection. The results suggest that a combination of multiple monoclonal antibodies may be the best strategy for treating future SARS-CoV-2 variant outbreaks.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Yu-Chieh Liao, Feng-Jui Chen, Min-Chieh Chuang, Han-Chieh Wu, Wan-Chen Ji, Guann-Yi Yu, Tsi-Shu Huang
Summary: The widely used amplicon-based approach for SARS-CoV-2 genome sequencing has limitations, including low sequence coverage and high resource requirements. To address these issues, the researchers proposed a single PCR method to efficiently detect spike gene mutations and developed a bioinformatic protocol for accurate variant calling of spike protein. Their approach showed high detection rates and robustness against different sequencing datasets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)