Review
Chemistry, Medicinal
Kuanglei Wang, Huicong Zhang, Yongshou Tian
Summary: This review covers influenza drugs, mutation types of neuraminidase, molecular mechanisms of drug resistance, strategies to enhance drug susceptibility, and alternative therapies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Public, Environmental & Occupational Health
Thiago das Chagas Sousa, Jessica Santa Cruz Carvalho Martins, Milene Dias Miranda, Cristiana Couto Garcia, Paola Cristina Resende, Cliomar A. A. Santos, Maria do Carmo Debur, Rodrigo Ribeiro Rodrigues, Andrea Cony Cavalcanti, Tatiana Schaffer Gregianini, Felipe Campos de Melo Iani, Felicidade Mota Pereira, Sandra Bianchini Fernandes, Jessylene de Almeida Ferreira, Katia Correa de Oliveira Santos, Fernando Motta, David Brown, Walquiria Aparecida Ferreira de Almeida, Marilda Mendonca Siqueira, Aline da Rocha Matos
Summary: This study evaluated the antiviral resistance of Brazilian influenza A virus strains and found a low prevalence of resistance markers, indicating that antiviral drugs are still effective. However, there is a need for strengthened surveillance of influenza resistance.
FRONTIERS IN PUBLIC HEALTH
(2022)
Article
Chemistry, Medicinal
Ruifang Jia, Jian Zhang, Chiara Bertagnin, Srinivasulu Cherukupalli, Wei Ai, Xiao Ding, Zhuo Li, Jiwei Zhang, Han Ju, Xiuli Ma, Arianna Loregian, Bing Huang, Peng Zhan, Xinyong Liu
Summary: The structural modifications at the 150-cavity of influenza virus neuraminidases can result in more potent oseltamivir derivatives, with compound 5c showing the most promising activity. In vitro and in vivo studies demonstrated low cytotoxicity and no acute toxicity of 5c, indicating its potential as a drug candidate.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Hongqian Zhao, Siyuan Jiang, Zhifan Ye, Hongxi Zhu, Baichun Hu, Peipei Meng, Yanmei Hu, Huicong Zhang, Kuanglei Wang, Jun Wang, Yongshou Tian
Summary: The study designed a series of oseltamivir derivatives bearing hydrazide fragment, successfully targeting the 150 cavity, showing potent activity and satisfactory metabolic stability. This provides an important reference for potent inhibition against the H274Y mutant of NAs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, General & Internal
Sofia Tejada, Miia Jansson, Candela Sole-Lleonart, Jordi Rello
Summary: Neuraminidase inhibitors (NAIs) therapy significantly reduced the time to clinical resolution, total influenza-related complications, acute otitis media and need for antibiotic treatment. While reductions in mortality, pneumonia, asthma exacerbations, and hospitalization rates only demonstrated a trend benefit with NAIs treatment. The most significant adverse event associated with NAIs was an increase in nausea and vomiting.
EUROPEAN JOURNAL OF INTERNAL MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Pengfei Wang, Babayemi O. Oladejo, Chenning Li, Lifeng Fu, Shanshan Zhang, Jianxun Qi, Xun Lv, Xuebing Li
Summary: Various strategies have been explored for developing new and efficient NA inhibitors, including modifying antiviral drugs and targeting specific amino acid residues. A compound bearing a 3-phenylamino group demonstrated superior activity in inhibiting multiple NAs and showed potent antiviral replication in vitro.
Article
Immunology
Takuji Komeda, Takahiro Takazono, Naoki Hosogaya, Eriko Ogura, Masakazu Fujiwara, Hideyuki Miyauchi, Yoshikazu Ajisawa, Shinpei Iwata, Hideaki Watanabe, Keiichi Honda, Yoshitake Kitanishi, Kanae Hara, Hiroshi Mukae
Summary: The study found that baloxavir may help reduce household transmission of influenza compared to oseltamivir. However, no similar reduction was shown in comparison to inhalant medications, which may be due to unmeasured confounding factors related to differences in administration route.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Plant Sciences
Zhigeng Wu, Sanjay Kumar Singh, Ruiqing Lyu, Sitakanta Pattanaik, Ying Wang, Yongqing Li, Ling Yuan, Yongliang Liu
Summary: In this study, researchers found that AtMYB12, a transcription factor in Arabidopsis, can effectively increase the production of flavonoids in licorice hairy roots. AtMYB12 induces the expression of genes involved in the phenylalanine/flavonoid pathway and reprograms carbohydrate metabolism to enhance flavonoid biosynthesis. Additionally, AtMYB12 activates the salicylic acid and jasmonic acid signaling pathways and upregulates WRKY transcription factors, possibly activating the plant defense pathways.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Multidisciplinary Sciences
Chuanxiong Nie, Marlena Stadtmueller, Badri Parshad, Matthias Wallert, Vahid Ahmadi, Yannic Kerkhoff, Sumati Bhatia, Stephan Block, Chong Cheng, Thorsten Wolff, Rainer Haag
Summary: This study demonstrates the topology-matched design of heteromultivalent nanostructures as potent and broad-spectrum virus entry inhibitors based on the host cell membrane. By transferring heteromultivalent binding moieties to nanostructures with a bowl-like shape matching the viral surface, the inhibitors show superior performance in virus propagation inhibition. With identified binding sites on the S protein of SARS-CoV-2, this approach holds promise in developing effective inhibitors to prevent coronavirus infection.
Article
Microbiology
Chiara Medaglia, Arnaud Charles-Antoine Zwygart, Paulo Jacob Silva, Samuel Constant, Song Huang, Francesco Stellacci, Caroline Tapparel
Summary: Influenza viruses have high genetic variability and can quickly develop resistance mutations. Combination therapy with two drugs can reduce the risk of resistance emergence. Combining interferon lambda with oseltamivir can delay the emergence of drug-resistant influenza virus variants.
Article
Virology
Weixu Zhang, Hefeng Xu, Shuxuan Guan, Chengmin Wang, Guoying Dong
Summary: This study analyzed the available NA protein sequences of H1N1 influenza viruses worldwide and found that 3.76% of H1N1 viruses currently harbor oseltamivir resistance, with the most common mutation being H274Y. Oseltamivir resistance is mainly found in humans, swine, and avian, and the resistance level peaked in 2007-2008 and quickly decreased in 2009. The study highlights the importance of globally monitoring oseltamivir resistance.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Chemistry, Physical
Chonnikan Hanpaibool, Matina Leelawiwat, Kaito Takahashi, Thanyada Rungrotmongkol
Summary: Influenza is a respiratory contagious disease infecting people worldwide, leading to a high number of infections and deaths. Drug resistance has developed in many subtypes of influenza due to high mutation rates, reducing the effectiveness of drugs like oseltamivir.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Multidisciplinary Sciences
Eun-Jung Song, Erica Espano, Sang-Mu Shim, Jeong-Hyun Nam, Jiyeon Kim, Kiho Lee, Song-Kyu Park, Chong-Kil Lee, Jeong-Ki Kim
Summary: The study found that the serine protease inhibitor aprotinin has inhibitory effects on a wide range of influenza virus subtypes, including avian influenza viruses and oseltamivir-resistant influenza viruses, and significantly increased survival rate in mice infected with a lethal dose of influenza virus. This suggests that aprotinin could be considered for development as a therapeutic agent against influenza.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Medicinal
Ruifang Jia, Jiwei Zhang, Fangyuan Shi, Anna Bonomini, Camilla Lucca, Chiara Bertagnin, Jian Zhang, Chuanfeng Liu, Huinan Jia, Yuanmin Jiang, Xiuli Ma, Arianna Loregian, Bing Huang, Peng Zhan, Xinyong Liu
Summary: Two series of oseltamivir derivatives were designed, synthesized, and evaluated for their ability to inhibit neuraminidase. Compound 43b showed weaker or slightly improved inhibitory activity against wild-type neuraminidases compared to oseltamivir carboxylate. However, it displayed significantly more potent activity against mutant neuraminidases and exhibited equivalent or more potent antiviral activities in cellular assays. Additionally, 43b possessed improved physicochemical properties and ADMET properties compared to oseltamivir carboxylate. Therefore, it is considered a promising lead compound for further investigation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Infectious Diseases
Naoki Tani, Naoki Kawai, Yong Chong, Takuma Bando, Norio Iwaki, Seizaburo Kashiwagi, Hideyuki Ikematsu
Summary: This study investigated the susceptibility of epidemic influenza viruses to neuraminidase inhibitors and the emergence of resistant viruses after treatment. The results suggest the continued effectiveness of these inhibitors for epidemic influenza in Japan. Treatment-emergent resistant viruses were detected after oseltamivir treatment.
JOURNAL OF INFECTION
(2022)
Article
Chemistry, Organic
Ba Wool Lee, Thi Kim Quy Ha, Eun Jin Park, Hyo Moon Cho, Byeol Ryu, Thi Phuong Doan, Hee Ju Lee, Won Keun Oh
Summary: Five unprecedented Caryophyllaceae-type cyclopeptides were isolated from Melicope pteleifolia leaves, showing strong antiviral activity against influenza A viruses, especially H1N1. Compound 3 exhibited the most potent inhibition effect against H1N1, with an EC50 of 2.57.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Plant Sciences
Hyo-Moon Cho, Mi Zhang, Eun-Jin Park, Ba-Wool Lee, Yeon-Joo Park, Hyun-Woo Kim, Ha-Thanh-Tung Pham, Young-Won Chin, Won-Keun Oh
Summary: This study discovered several flavonostilbenes from the stems of Rhamnoneuron balansae, and evaluated their effects on SIRT1 deacetylase activity. One compound showed promising anti-aging activity in vitro.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Plant Sciences
Trong-Tuan Dao, Katherine Williams, Kate M. J. de Mattos-Shipley, Zhongshu Song, Yuiko Takebayashi, Thomas J. Simpson, James Spencer, Andrew M. Bailey, Christine L. Willis
Summary: Three new polyketide-derived natural products and six known metabolites were isolated from fermentation of the fungus Cladobotryum sp. Their antibacterial activities against Staphylococcus aureus strains revealed the importance of unsaturated decalins for biological activity.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Plant Sciences
Huong Pham, Thi Phuong Doan, Hyun Woo Kim, Tae Wan Kim, So-Yeon Park, Hangnun Kim, Mina Lee, Ki Hyun Kim, Won Keun Oh, Young Woon Lim, Kyo Bin Kang
Summary: Microbial cocultivation is a strategy to induce the biosynthesis of specialized metabolites. In this study, the coculture of Phellinus orientoasiaticus and Xylodon flaviporus was found to induce the production of multiple metabolites. The isolated compounds did not exhibit antifungal activity or cytotoxicity.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Chemistry, Organic
Joonseok Jang, Jinwoo Lee, Seok Beom Lee, Seung Hyun Choi, Eun Jin Park, Sang Jun Yoon, Joon Soo An, Dong-Chan Oh, Won Keun Oh, Suckchang Hong
Summary: In this study, we reported the total synthesis of melicoptelines C-E, which exhibited anti-influenza activity. The core 3a-hydroxy HPIs were synthesized and then coupled and cyclized to obtain the target compounds. Among them, melicopteline E showed the most potent inhibition of cytopathic effects.
Article
Chemistry, Medicinal
Byeol Ryu, Eun-Jin Park, Thi-Phuong Doan, Hyo-Moon Cho, Jin-Pyo An, Thi-Linh-Giang Pham, Ha-Thanh-Tung Pham, Won-Keun Oh
Summary: Ten phenolic constituents, including three new macrocyclic glycosides and a new phenolic glycoside, were isolated from the leaves of Heliciopsis terminalis. These compounds showed stimulatory effects on glucose uptake and some of them activated the AMPK signaling pathway.
Article
Chemistry, Medicinal
Hee-Ju Lee, Eun-Jin Park, Byeol Ryu, Hyo-Moon Cho, Duc-Trong Nghiem, Ha-Thanh-Tung Pham, Cheol-Ho Pan, Won-Keun Oh
Summary: This study isolated new benzylisoquinoline alkaloid derivatives from Limacia scandens and tested their autophagy-regulating activity. Several compounds showed potential autophagy inhibition activity, providing potential candidates for developing natural autophagy inhibitors.
Article
Biochemistry & Molecular Biology
Ha-Thanh-Tung Pham, Eun-Jin Park, Byeol Ryu, Hee-Ju Lee, Thi-Phuong Doan, Hyo-Moon Cho, Thi-Linh-Giang Pham, Won-Keun Oh
Summary: Chemical investigation of Gymnema latifolium led to the discovery of seven undescribed 23-glycosyl oleanane triterpenoids, gymlatinosides GLF1-GLF7, and two known compounds, gymnemosides D and E. The structures of these compounds were determined using various spectroscopic methods. The extract of G. latifolium and all isolated compounds significantly increased glucose uptake in 3T3-L1 adipocytes at a concentration of 20 μM. Among them, gymlatinosides GLF2 and gymlatinosides GLF4 exhibited particularly potent dose-dependent effects on glucose uptake. Further investigation revealed that gymlatinosides GLF2 upregulated the expression of phosphorylated AMPK (p-AMPK) at a concentration of 20 μM. These findings suggested that gymlatinosides GLF2 may enhance glucose uptake by regulating the AMPK signaling pathway.
Article
Biochemistry & Molecular Biology
Thi-Phuong Doan, Eun-Jin Park, Byeol Ryu, Hyo-Moon Cho, Sang -Jun Yoon, Gwan-Young Jung, Phuong-Thien Thuong, Won-Keun Oh
Summary: A phytochemical investigation of Alchornea rugosa leaves revealed eight undescribed guanidine-flavanol conjugates named rugonines A-H. The chemical structures of these compounds were comprehensively elucidated using NMR spectroscopy, HRESIMS, and circular dichroism (CD) analysis. In autophagosome formation experiments conducted in HEK293 cells expressing GFP-LC3, rugonines D-G showed potential autophagy inhibitory activity.
Article
Agriculture, Dairy & Animal Science
Eun Jin Park, Ba Wool Lee, Byeol Ryu, Hyo Moon Cho, Seong Kyun Kim, Seong-Sik Yoo, Eunhee Kim, Won Keun Oh
Summary: This study aimed to discover an anti-influenza herbal mixture and evaluate its antiviral activity against avian influenza. Three different medicinal plants with distinct medicinal purposes were selected and formulated into a combination, which showed potent inhibitory effects on the virus and reduced mortality and virus titers in chickens infected with avian influenza.
Article
Environmental Sciences
Hyeon-Jeong Lee, Minsik Kang, Junghyun Son, Hophil Min, Sangwon Cha, Han Bin Oh, Won Keun Oh, Jaeick Lee
Summary: Phenols are important environmental endocrine disruptors with potential adverse health effects. A comprehensive and sensitive analytical method for multiple classes of phenols was developed by investigating the influence of mobile phase compositions in LC-ESI-MS/MS analysis. This method allowed for the concurrent ionization of all phenols and significantly improved the analytical sensitivity for certain phenols.
ENVIRONMENTAL RESEARCH
(2023)
Article
Plant Sciences
Thi-Phuong Doan, Mi Zhang, Eun-Jin Park, Jorge-Eduardo Ponce-Zea, Van-Hieu Mai, Hyo-Moon Cho, Ha-Thanh-Tung Pham, Won-Keun Oh
Summary: This study investigated the chemical components of avocado seeds and discovered several new alkaloids. The bioactivities of these compounds on SIRT1 were evaluated, and one compound showed the most potent activation effect, suggesting its potential as an anti-aging agent.
JOURNAL OF NATURAL PRODUCTS
(2023)
Correction
Plant Sciences
Huong T. Pham, Thi Phuong Doan, Hyun Woo Kim, Tae Wan Kim, So-Yeon Park, Hangun Kim, Mina Lee, Ki Hyun Kim, Won Keun Oh, Young Woon Lim, Kyo Bin Kang
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Biochemistry & Molecular Biology
Hee Ju Lee, Mi Zhang, Thi Phuong Doan, Eun-Jin Park, Duc-Trong Nghiem, Ha-Thanh-Tung Pham, Cheol-Ho Pan, Won-Keun Oh
Summary: Seven undescribed chemicals, including two syringylglycerol derivatives, two cyclopeptides, one tigliane analogue, and two chromone derivatives, were isolated from the stems of Limacia scandens during the screening of senotherapeutics from natural products. The structures of these compounds were determined through spectroscopic data analysis. Testing these compounds in replicative senescent human dermal fibroblasts revealed that one tigliane and two chromone derivatives exhibited senolytic activity, selectively eliminating senescent cells. In particular, 2-{2-[(3'-O-beta-D-glucopyranosyl) phenyl]ethyl}chromone showed potential as a senotherapeutic agent by inducing HDF death, inhibiting the activity of senescence-associated beta-galactosidase (SA-beta-gal), and expressing senescence-associated secretory phenotype (SASP) factors.
Article
Biochemistry & Molecular Biology
Byeol Ryu, Eun-Jin Park, Thi-Phuong Doan, Hyo-Moon Cho, Jorge-Eduardo Ponce-Zea, Van-Hieu Mai, Vahideh Oveissi, Won-Keun Oh
Summary: Autophagy inhibitory activity was found in unique oligomeric flavonoids derived from the roots of Lindera erythrocarpa. The structures and configurations of these compounds were determined using various techniques. The study revealed that these compounds can inhibit autophagy by blocking the fusion process between autophagosome and lysosome.
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
