Article
Immunology
S. Scott Sutton, Joseph Magagnoli, Tammy Cummings, James Hardin
Summary: This study explored the association between antibiotics, antivirals, and hospitalization among influenza patients. The results showed that patients treated with antivirals, antibiotics, or both had a lower risk of hospitalization within 30 days compared to those without treatment. Additionally, patients treated with both antibiotics and antivirals had a lower risk of respiratory hospitalization within 30 days compared to those with antivirals alone.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Immunology
Brian D. Stamm, John Tamerius, Sush Reddy, Shari Barlow, Caroline Hamer, Ashley Kempken, Maureen Goss, Cecilia He, Cristalyne Bell, Mitchell Arnold, Mary Checovich, Emily Temte, Derek Norton, Guanhua Chen, Jeffrey Baltus, Emily S. Gurley, Jonathan L. Temte
Summary: The use of rapid influenza diagnostic tests (RIDTs) in urgent care clinics has a significant impact on clinician decision-making regarding diagnosis and treatment, resulting in improved patient outcomes, reduced influenza burden, and decreased antibiotic resistance threat.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Infectious Diseases
Azfar Ishaqui, Amer Hayat Khan, Syed Azhar Syed Sulaiman, Muhammad Taher Alsultan, Irfanullah Khan
Summary: The study concluded that early initiation of antibiotic therapy in combination with oseltamivir was more efficacious in preventing influenza B-associated complications compared to oseltamivir alone.
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
(2021)
Article
Microbiology
Andy Hesketh, Giselda Bucca, Colin P. Smith, Hee-Jeon Hong
Summary: Dalbavancin, vancomycin, and chlorobiphenyl-vancomycin are glycopeptide antibiotics with similar structures and modes of action, but they induce different gene expression patterns and have diverse impacts on bacterial cell wall biosynthesis and other physiological processes.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Oleksandr Yushchuk, Kseniia Zhukrovska, Bohdan Ostash, Victor Fedorenko, Flavia Marinelli
Summary: Glycopeptide antibiotics (GPAs) are successful antimicrobials that inhibit cell-wall biosynthesis in Gram-positive bacteria. Self-resistance genes in GPA producers are the primary source of GPA resistance genes spreading among pathogenic bacteria. The role of Tei3 sensor histidine kinase in GPA resistance in Actinoplanes teichomyceticus has been intensively studied and a possible co-evolution scenario for GPA-resistance and biosynthetic genes in A. teichomyceticus has been proposed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Infectious Diseases
Torgun Waehre, Gro Tunheim, Johanna Eva Bodin, Ida Laake, Dag Kvale, Anne-Marte Bakken Kran, Hanne Brekke, Ragnhild Loken, Fredrik Oftung, Siri Mjaaland, Anne Margarita Dyrhol-Riise
Summary: This study investigated the clinical characteristics and treatment practice in hospitalized adult influenza patients, and found that the majority of influenza patients were elderly and only a few required intensive care unit treatment. A high clinical risk score on admission was associated with severe outcomes. Currently, less than 40% of patients receive antiviral therapy, while the majority are treated with antibiotics, indicating the potential for optimizing treatment strategies.
INFECTIOUS DISEASES
(2022)
Article
Chemistry, Multidisciplinary
Yifei Song, Jingkai Zhang, Yue Fei, Zhangjian Huang, Xiaoxuan Liu, Li-Li Li
Summary: In this study, a glycopeptide-based antibiotic nano-adjuvant (GalAc-2) was proposed to enhance the antibacterial activity of antibiotics by inhibiting biofilm formation. Experimental results showed that GalAc-2 synergistically inhibited bacterial biofilm formation with antibiotics, significantly reduced abscess formation and immune cell infiltration, which suggests its potential in enhancing antibiotic sensitization and extending the lifetime of antibiotics.
SCIENCE CHINA-CHEMISTRY
(2022)
Article
Infectious Diseases
Andres Andreo-Vidal, Elisa Binda, Victor Fedorenko, Flavia Marinelli, Oleksandr Yushchuk
Summary: The global health security is challenged by the spread of antimicrobial resistance, affecting even glycopeptide antibiotics. Research has shown that GPA resistance determinants can be found not only in GPA producers, but also in non-producers, indicating a co-evolution of different vlgs.
Review
Virology
Mostafa Javanian, Mohammad Barary, Sam Ghebrehewet, Veerendra Koppolu, VeneelaKrishnaRekha Vasigala, Soheil Ebrahimpour
Summary: Influenza is an acute viral respiratory infection that affects all age groups and is associated with high mortality. Vaccination is the most effective method for prevention, but antiviral drugs are also available for treatment.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Article
Chemistry, Multidisciplinary
Anja Greule, Thierry Izore, Daniel Machell, Mathias H. Hansen, Melanie Schoppet, James J. De Voss, Louise K. Charkoudian, Ralf B. Schittenhelm, Jeffrey R. Harmer, Max J. Cryle
Summary: Cytochrome P450 enzymes are enzymes that can perform oxidative reactions using heme. However, some of these enzymes can be damaged by oxidation, leading to decreased enzyme activity. Research has shown that the heme orientation in the active site of certain cytochrome P450 enzymes may contribute to this oxidative damage.
FRONTIERS IN CHEMISTRY
(2022)
Article
Immunology
James W. Antoon, Matt Hall, James A. Feinstein, Kathryn E. Kyler, Samir S. Shah, Sonya Tang Girdwood, Jennifer L. Goldman, Carlos G. Grijalva, Derek J. Williams
Summary: This study investigated the concordance of antiviral treatment in children at high risk for influenza complications and found that 42% did not receive guideline-concordant antiviral treatment. Further research is needed to identify barriers to appropriate antiviral use in this vulnerable population.
CLINICAL INFECTIOUS DISEASES
(2023)
Review
Virology
Yaqin Bai, Jeremy C. Jones, Sook-San Wong, Mark Zanin
Summary: Hemagglutinin and neuraminidase are critical parts of influenza viruses, serving as targets for immune response and antiviral drugs. Neuraminidase inhibitors like oseltamivir are commonly used against influenza, while antivirals targeting hemagglutinin are newer with a higher resistance threshold.
Review
Immunology
Frederick G. Hayden, Jason Asher, Benjamin J. Cowling, Aeron C. Hurt, Hideyuki Ikematsu, Klaus Kuhlbusch, Annabelle Lemenuel-Diot, Zhanwei Du, Lauren Ancel Meyers, Pedro A. Piedra, Takahiro Takazono, Hui-Ling Yen, Arnold S. Monto
Summary: Studies indicate that prompt antiviral treatment can reduce the risk of influenza virus transmission to contacts, especially in household settings. However, reported effects vary widely across studies. Additionally, all approved classes of influenza antivirals carry a potential risk of transmitting drug-resistant variants.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Chemistry, Medicinal
Vladimir Vimberg, Leona Zieglerova, Aninda Mazumdar, Zsolt Szucs, Aniko Borbas, Pal Herczegh, Gabriela Balikova Novotna
Summary: This paper compares the in vitro activities of two new semisynthetic glycopeptide antibiotics with two clinically used glycopeptide antibiotics, finding that the new antibiotics effectively kill various states of Staphylococcus aureus cells.
Article
Microbiology
Paulina Koszalka, Ankita George, Vijaykrishna Dhanasekaran, Aeron C. Hurt, Kanta Subbarao
Summary: Combination therapy with influenza drugs baloxavir and oseltamivir can reduce the selection of viruses with reduced drug susceptibility. In animal models, combination therapy and monotherapy have similar effectiveness in reducing viral titers, but combination therapy can decrease the selection of viruses with reduced susceptibility to baloxavir.
Article
Pharmacology & Pharmacy
Iwona E. Glowacka, Katarzyna Gawron, Dorota G. Piotrowska, Mirthe Graus, Graciela Andrei, Dominique Schols, Robert Snoeck, Anita Camps, Emiel Vanhulle, Kurt Vermeire
Summary: In this study, a series of 48 hybrids were synthesised and evaluated for antiviral activity. The hybrids contained a diethoxyphosphoryl group connected to the triazole moiety via ethylene or propylene linker, and substituted benzyl or benzoyl function in the quinazoline-2,4-dione moiety. The hybrids showed potent antiviral activities against Respiratory Syncytial Virus (RSV), with some weak activity against varicella zoster virus and human cytomegalovirus.
ANTIVIRAL RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Nora Debreczeni, Judit Hotzi, Miklos Bege, Miklos Lovas, Erika Mezo, Ilona Bereczki, Pal Herczegh, Lorand Kiss, Aniko Borbas
Summary: The first concise and efficient synthesis of fluorine-containing morpholino nucleosides has been developed. One strategy involves oxidative ring cleavage of vicinal diol units in uridine, cytidine, adenosine, and guanosine derivatives, followed by cyclization of dialdehyde intermediates with fluorinated primary amines. Another approach includes cyclization of diformyl intermediates with ammonia source, followed by dithiocarbamate formation and desulfurization-fluorination to yield morpholine-based nucleoside analogues with N-CF3 elements.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Medicinal
Xu Ling, Qing-Qing Hao, Wen-Juan Huang, Christophe Pannecouque, Erik De Clercq, Shuai Wang, Fen-Er Chen
Summary: A series of S-N3-DABO derivatives F1-F31 were developed as novel non-nucleoside reverse transcriptase inhibitors (NNRTIs) by substituting the cyano group of S-CN-DABOs with azide group. These compounds showed significantly increased potency against wild-type HIV-1 and mutant strains. The best compound F10 exhibited a significant improvement in potency and selectivity compared to the parent compound B1, with enhanced activity against mutant strains and no significant inhibition of hERG, CYP, and acute toxicity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Wei Ming, Wen-Long Lu, Christophe Pannecouque, Jiong Chen, Hai-Feng Wang, Ya-Qi Xiao, Sha Hu, Shuang-Xi Gu, Yuan-Yuan Zhu, Fen-Er Chen
Summary: The hybrids of delavirdine and piperdin-4-yl-aminopyrimidine (DPAPYs) were synthesized and evaluated for their anti-HIV activities and inhibitory activities against HIV-1 reverse transcriptase. The results showed that all the compounds demonstrated moderate to excellent potency against wild-type HIV-1 and specific RT inhibitory activity. Compound 4d exhibited the most potent activity against wild-type HIV-1 and showed good to excellent potency against various HIV-1 mutants.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Da Feng, Hao Lin, Liyang Jiang, Jiaojiao Dai, Xiaoying Zhang, Zhongxia Zhou, Yanying Sun, Zhao Wang, Erik De Clercq, Christophe Pannecouque, Dongwei Kang, Peng Zhan, Xinyong Liu
Summary: A series of disubstituted pyrimidine-5-carboxamide derivatives were designed by introducing an amide moiety to the central core of the lead etravirine using crystallographic overlay-based molecular hybridization strategy. These compounds exhibited promising antiviral activities against wild-type and NNRTIs-resistant strains of HIV-1, with compound 21c showing the most potent activity. The compound was proven to target reverse transcriptase and could serve as a lead for developing novel HIV-1 NNRTIs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Jianyang Han, Jakob Arnold, Christophe Pannecouque, Graciela Andrei, Robert Snoeck, Clemens Richert
Summary: Strongly pairing ethynylpyridone C-nucleosides are being explored as substitutes for thymidine in oligonucleotides. However, the strong lipophilicity of ethynylpyridone has been found to limit its antiviral activity. Two strategies are being pursued to overcome this issue, including replacing the ethynyl group with a cyano group and using less lipophilic amino acid esters in a phosphoramidate prodrug design. These findings contribute to the development of next-generation pyridone C-nucleosides as potential antivirals.
HELVETICA CHIMICA ACTA
(2023)
Article
Biochemistry & Molecular Biology
Zhao-Hui Wen, Meng-Meng Wang, Ling-Yun Li, Piet Herdewijn, Robert Snoeck, Graciela Andrei, Zhao-Peng Liu, Chao Liu
Summary: In this study, the synthesis of lipid prodrugs of beta-D-N4-hydroxycytidine (NHC) and a 3'-fluoro modified NHC analogue was reported, and their antiviral activity against five variants of SARS-CoV-2 was evaluated. The lipid prodrugs showed potent antiviral activity against the tested variants, with comparable or higher EC50 values than remdesivir and molnupiravir. The 3'-F analogue of NHC only exhibited minor antiviral activity against the Omicron variant, while no activity was observed against other variants. The promising antiviral data of the lipid prodrugs suggest their potential as new anti-SARS-CoV-2 drugs.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
M. P. Paramonova, E. S. Gureeva, A. A. Ozerov, R. Snoeck, G. Andrei, D. A. Aleksandrov, A. L. Khandazhinskaya, M. S. Novikov, S. N. Kochetkov
Summary: A new series of 1-[ω-(bromophenoxy)alkyl]-uracil derivatives containing various fragments were synthesized and tested for their antiviral activity against human cytomegalovirus. It was found that the compound with a bridge of five methylene groups exhibited high anti-cytomegalovirus activity in vitro.
DOKLADY BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Pharmacology & Pharmacy
Evelien Vanderlinden, Arnaud Boonen, Sam Noppen, Geert Schoofs, Maya Imbrechts, Nick Geukens, Robert Snoeck, Annelies Stevaert, Lieve Naesens, Graciela Andrei, Dominique Schols
Summary: PRO-2000, a sulfonated polyanionic compound, has anti-SARS-CoV-2 activity by blocking the entry pathway and inhibiting the binding of the S protein to its receptor. It can potentially inhibit a broad range of SARS-CoV-2 variants.
ANTIVIRAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Polina Kamzeeva, Ivan Petushkov, Ekaterina Knizhnik, Robert Snoeck, Yuri Khodarovich, Ekaterina Ryabukhina, Vera Alferova, Artur Eshtukov-Shcheglov, Evgeny Belyaev, Julia Svetlova, Tatiana Vedekhina, Andrey Kulbachinskiy, Anna Varizhuk, Graciela Andrei, Andrey Aralov
Summary: Emerging and re-emerging viruses cause global outbreaks and epidemics, highlighting the need for new antiviral drugs. Researchers synthesized and evaluated nucleoside analogs and their derivatives, finding that one compound had antiviral activity against coronaviruses and specifically inhibited biocondensate formation important for replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Cardiac & Cardiovascular Systems
J. Kaes, E. Vanhulle, L. Seldeslachts, C. Hooft, H. Beeckmans, X. Jin, P. Kerckhof, J. Van Slambrouck, D. Van Raemelonck, G. Vande Velde, L. Naesens, D. Schols, L. J. Ceulemans, R. Vos, K. Vertneire, B. M. Vanaudenaerde
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2023)
Article
Chemistry, Organic
Miklos Bege, Mihaly Herczeg, Ilona Bereczki, Nora Debreczeni, Attila Benyei, Pal Herczegh, Aniko Borbas
Summary: In this study, we describe the stereoselective synthesis of a novel type of nucleoside analogue with a conformationally constrained structure. The sugar part of the analogue was replaced by a new symmetrical tricycle consisting of a morpholine ring condensed with two imidazolidines. The synthesis involved the reaction of dialdehydes obtained from protected nucleosides with a new method-produced trisamine reactant, followed by cascade tricyclization to form the desired triaza-tricyclic derivatives.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Shujing Xu, Lin Sun, Waleed A. Zalloum, Xujie Zhang, Tianguang Huang, Dang Ding, Yucen Tao, Fabao Zhao, Shenghua Gao, Dongwei Kang, Erik De Clercq, Christophe Pannecouque, Alexej Dick, Simon Cocklin, Xinyong Liu, Peng Zhan
Summary: A series of phenylalanine derivatives were designed and synthesized by modifying the structure of PF74, which showed potent anti-HIV activity. Compound 7n exhibited 6.25-fold better anti-HIV-1 activity than PF74, while 7h showed nearly 139 times improved anti-HIV-2 activity. The binding target of 7n was identified as HIV-1 capsid protein, and it inhibited virus replication through binding to a vital CA assembly interface.
CHINESE CHEMICAL LETTERS
(2023)
Article
Chemistry, Medicinal
Shujing Xu, Lin Sun, Michael Barnett, Xujie Zhang, Dang Ding, Anushka Gattu, Dazhou Shi, Jamie R. H. Taka, Wenli Shen, Xiangyi Jiang, Simon Cocklin, Erik De Clercq, Christophe Pannecouque, David C. Goldstone, Xinyong Liu, Alexej Dick, Peng Zhan
Summary: Optimization of compound 11L led to the discovery of novel HIV capsid modulators, quinazolin-4-one-bearing phenylalanine derivatives, which exhibited potent antiviral activities against both HIV-1 and HIV-2. These derivatives occupied multiple pockets at the binding site and displayed a dual-stage inhibition profile, making them potential candidates for HIV capsid modulation and paving the way for future anti-HIV drug design.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Rasha Z. Batran, Ahmed Sabt, Mohammed A. Khedr, Abdou K. Allayeh, Christophe Pannecouque, Asmaa F. Kassem
Summary: A series of 4-phenylcoumarin derivatives were synthesized and evaluated for their antiviral activities against HIV-1 and HIV-2, as well as their inhibitory effects on HIV-1 reverse transcriptase. Compound 8b and derivative 4c showed the best inhibition activity against wild-type HIV-1, with compound 8b exhibiting comparable effect to the reference NNRTI Efavirenz. Structure-activity relationship study revealed the importance of 6-chloro and 4-phenyl substituents, as well as the 5-atoms linker at position 7 of the coumarin scaffold.
BIOORGANIC CHEMISTRY
(2023)
