A broad influenza virus inhibitor acting via IMP dehydrogenase and in synergism with ribavirin

Vanderlinden, Evelien; Marchand, Arnaud; Berwaer, Ria Van; Dam, Wim van; Arzel, Philippe; Klaassen, Hugo; Persoons, Leentje; Chaltin, Patrick; Naesens, Lieve

doi:10.1016/j.antiviral.2021.105208

Cited by 7 publications

(10 citation statements)

References 26 publications

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“…We then turned our attention to α,β-unsaturated lactone (Table 3). Modification of the unsaturated double bond by means of Heck reaction, Michael addition reaction, or hydrogenation caused either complete losses (13−16) or a distinct decrease (17) in inhibitory activity. These results revealed that the terminal olefinic bond was essential.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Modular Biomimetic Strategy Enables Discovery and SAR Exploration of Oxime Macrocycles as Influenza A Virus (H1N1) Inhibitors

Xu,

Gong,

Zhang

et al. 2024

J. Med. Chem.

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Although vaccination remains the prevalent prophylactic means for controlling Influenza A virus (IAV) infections, novel structural antivirus small-molecule drugs with new mechanisms of action for treating IAV are highly desirable. Herein, we describe a modular biomimetic strategy to expeditiously achieve a new class of macrocycles featuring oxime, which might target the hemagglutinin (HA)-mediated IAV entry into the host cells. SAR analysis revealed that the size and linker of the macrocycles play an important role in improving potency. Particularly, as a 14-membered macrocyclic oxime, 37 exhibited potent inhibitory activity against IAV H1N1 with an EC50 value of 23 nM and low cytotoxicity, which alleviated cytopathic effects and protected cell survival obviously after H1N1 infection. Furthermore, 37 showed significant synergistic activity with neuraminidase inhibitor oseltamivir in vitro.

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Section: ■ Results and Discussionmentioning

confidence: 99%

“…1 13 C NMR (126 MHz, chloroform-d) δ 176.0, 172.8, 168.9, 163.8, 140.3, 137.5, 132.2 (q, J = 32.3 Hz), 127.4, 126.3 (q, J = 3.3 Hz), 123.9 (q, J = 3.5 Hz), 123.7 (q, J = 272. 4 (17). Off-white solid (40%).…”

Section: E ) -5 -( M E T H O X Y I M I N O ) -4 4 -D I M E T H Y L -...mentioning

confidence: 99%

Modular Biomimetic Strategy Enables Discovery and SAR Exploration of Oxime Macrocycles as Influenza A Virus (H1N1) Inhibitors

Xu,

Gong,

Zhang

et al. 2024

J. Med. Chem.

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“…Evidence shows that IMPDH inhibitors (Figure 2) also present antiviral activity as well as anticancer activities, Table 1. [47,54,[91][92][93] Ribavirin, an important molecule used as the standard of care in many viral infections, is a reported IMPDH inhibitor; [94] however, its antiviral profile is a result not only of de novo nucleotide synthesis inhibition but also of other different mechanisms of action. [95][96][97] Mycophenolic acid (MPA) is another approved IMPDH inhibitor that is used as an immunosuppressant in kidney and liver transplantations.…”

Section: Purine Biosynthesis Inhibitorsmentioning

confidence: 99%

The synergy between nucleotide biosynthesis inhibitors and antiviral nucleosides: New opportunities against viral infections?

Miranda

2022

Archiv der Pharmazie

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5ʹ-Phosphorylated nucleoside derivatives are molecules that can be found in all living organisms and viruses. Over the last century, the development of structural analogs that could disrupt the transcription and translation of genetic information culminated in the development of clinically relevant anticancer and antiviral drugs.However, clinically effective broad-spectrum antiviral compounds or treatments are lacking. This viewpoint proposes that molecules that inhibit nucleotide biosynthesis may sensitize virus-infected cells toward direct-acting antiviral nucleosides. Such potentially synergistic combinations might allow the repurposing of drugs, leading to the development of new combination therapies.

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“…[7,8] Ribavirin is effective against influenza viruses. [9] Studies have shown that ribavirin significantly reduces lung lesions and pulmonary virus titers by inhibiting viral replication. [10] However, because of the widespread use of antiinfluenza drugs, varying degrees of drug resistance have been observed.…”

Section: Introductionmentioning

confidence: 99%

“…At present, the widely used antiviral drugs are:M2 proton channel blockers (amantadine and rimantadine), neuraminidase (NA) inhibitors, and broad‐spectrum antivirals(ribavirin) [7,8] . Ribavirin is effective against influenza viruses [9] . Studies have shown that ribavirin significantly reduces lung lesions and pulmonary virus titers by inhibiting viral replication [10] .…”

Section: Introductionmentioning

confidence: 99%

Mechanism of the Anti‐Influenza Functions of Guizhi Granules Based on Network Pharmacology, Molecular Docking, and in Vitro Experiments

Wei¹,

Li²,

Liu³

et al. 2023

Chemistry & Biodiversity

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Guizhi granules mainly treat colds and improve overall health. They are widely used in clinical practice, but their protective effect and anti-inflammatory mechanism against influenza are unclear. In this study, the therapeutic effect of Guizhi granules on influenza was verified in vitro. The active compounds, targets, and cellular pathways of Guizhi granules against influenza were predicted using network pharmacology. The protein-protein interaction and component-target networks identified 5 core targets (JUN, TNF-α, RELA, AKT1, and MAPK1) and components (dihydrocapsaicin, kumatakenin, calycosin, licochalcone A, and berberine). GO and KEGG enrichment analyses revealed the anti-influenza pathways of Guizhi granules as antiviral and anti-inflammatory pathways. Molecular docking further verified that the core targets and components have good or strong binding activity. Therefore, the active ingredients, targets, and molecular mechanisms of Guizhi granules involved in influenza treatment were elucidated.

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A broad influenza virus inhibitor acting via IMP dehydrogenase and in synergism with ribavirin

Cited by 7 publications

References 26 publications

Modular Biomimetic Strategy Enables Discovery and SAR Exploration of Oxime Macrocycles as Influenza A Virus (H1N1) Inhibitors

Modular Biomimetic Strategy Enables Discovery and SAR Exploration of Oxime Macrocycles as Influenza A Virus (H1N1) Inhibitors

The synergy between nucleotide biosynthesis inhibitors and antiviral nucleosides: New opportunities against viral infections?

Mechanism of the Anti‐Influenza Functions of Guizhi Granules Based on Network Pharmacology, Molecular Docking, and in Vitro Experiments

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