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
Biochemistry & Molecular Biology
Sphamandla E. Mtambo, Samuel C. Ugbaja, Hezekiel M. Kumalo
Summary: The emergence of the avian influenza virus H7N9 in China has raised concerns due to its potential to cause serious respiratory diseases in humans. Studies have shown that a specific mutation in the virus can lead to resistance to the antiviral drug peramivir. Molecular dynamics approaches have been used to evaluate the impact of this mutation on drug resistance, revealing changes in the binding affinity and interactions with the drug.
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, 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)
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
Biochemistry & Molecular Biology
Samuel C. Ugbaja, Sphamandla E. Mtambo, Aganze G. Mushebenge, Patrick Appiah-Kubi, Bahijjahtu H. Abubakar, Mthobisi L. Ntuli, Hezekiel M. Kumalo
Summary: The use of vaccinations and antiviral medications has become popular for treating avian influenza H7N9 virus. This study investigated the impact of the E119V mutation on the resistance of the virus to oseltamivir. Molecular dynamics simulations showed that the oseltamivir-wildtype complex was more thermodynamically stable than the oseltamivir-E119V mutant complex. The E119V mutation resulted in lower conformational stability and weaker protein-ligand interactions.
Article
Biochemistry & Molecular Biology
Yusuke Kato, Kazuhiro Takahashi, Fuyu Ito, Shoichi Suzuki, Kiyoshi Fukui, Masakazu Mimaki, Kazuo Suzuki
Summary: This study identified oseltamivir-resistant influenza B samples with common amino acid substitutions that decrease the affinity of oseltamivir to neuraminidase. These substitutions, N340D and E358K, located far from the binding site, rearranged hydrogen bond networks and altered the electrostatic potential map, indirectly influencing affinity through novel mechanisms. These findings may inform the development of drugs for treating oseltamivir-resistant virus infections.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biotechnology & Applied Microbiology
Erik Skog, Marie Nykvist, Mahmoud M. Naguib, Michelle Wille, Caroline Brojer, Viktoria Agarwal, Patrik Ellstrom, Gabriel Westman, Ake Lundkvist, Josef D. Jarhult
Summary: This study investigates the potential transmission of OC-resistant avian influenza virus from mallards to chickens. The results show that even OC-resistant viruses can spread from ducks to chickens and replicate in chickens. However, these viruses cannot sustain transmission in chickens, likely due to insufficient adaptation to the chicken host.
JOURNAL OF GENERAL VIROLOGY
(2023)
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
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
Chemistry, Medicinal
Jiqing Ye, Lin Lin, Jinyi Xu, Paul Kay-sheung Chan, Xiao Yang, Cong Ma
Summary: Oseltamivir is a successful neuraminidase inhibitor in current anti-influenza therapy, and novel derivatives with pyrazole moiety show promising activity against NA. ADME evaluation indicates these derivatives have drug-like properties with better oral absorption and cell permeability compared to Oseltamivir carboxylate. Molecular docking studies confirm the interaction between the derivatives and NA enzyme active site as well as 150-cavity, providing valuable information for further optimization.
Article
Multidisciplinary Sciences
Maki Kiso, Yuri Furusawa, Ryuta Uraki, Masaki Imai, Seiya Yamayoshi, Yoshihiro Kawaoka
Summary: In this study, the authors characterized mutant viruses with reduced sensitivity to nirmatrelvir, an oral antiviral agent that targets SARS-CoV-2. They found that these mutant viruses showed a slower growth rate and attenuated phenotypes in infection models. However, it is important to closely monitor the emergence of nirmatrelvir-resistant SARS-CoV-2 variants as they could potentially become dominant.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Svetlana Svyatchenko, Natalia Goncharova, Vasiliy Y. Marchenko, Natalia P. Kolosova, Alexander N. Shvalov, Valentina L. Kovrizhkina, Alexander G. Durymanov, Galina S. Onkhonova, Tatyana Tregubchak, Ivan M. Susloparov, Andrey S. Gudymo, Tatyana N. Ilyicheva, Alexander B. Ryzhikov
Summary: This study assessed antiviral susceptibility of influenza A(H5N8) viruses in Russia, finding that only one strain had amino acid substitution related to adamantane resistance, and another strain had a substitution associated with reduced inhibition by oseltamivir. Global analysis revealed a small percentage of H5N8 viruses showing resistance to antiviral agents.
ANTIVIRAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Jiwei Zhang, Chuanfeng Liu, Ruifang Jia, Xujie Zhang, Jian Zhang, Chiara Bertagnin, Anna Bonomini, Laura Guizzo, Yuanmin Jiang, Huinan Jia, Shuzhen Jia, Xiuli Ma, Arianna Loregian, Bing Huang, Peng Zhan, Xinyong Liu
Summary: Introducing structurally diverse benzyl side chains at the C5-NH2 position of oseltamivir improves its binding affinity with neuraminidase and anti-influenza activity. We designed and synthesized novel oseltamivir derivatives with different N-heterocycle substituents that induce opening of the 150-loop of group-2 neuraminidases. Compound 6k showed broad-spectrum activity against wild-type neuraminidases and enhanced activity against H3N2 compared to oseltamivir carboxylate and zanamivir.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Avishak Sarker, Zichen Gu, Lu Mao, Yongzhuang Ge, Duoduo Hou, Jieyu Fang, Zhanyong Wei, Zhenya Wang
Summary: Influenza is a century-old disease that poses challenges to humans due to its mutating nature, seasonal epidemics, and occasional pandemics. The limited effectiveness of strain-specific vaccines and the growing drug resistance to anti-influenza drugs call for the development of novel drugs with broad reactivity, higher bioavailability, easier administration, and fewer side effects.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
