Novel spirothiazamenthane inhibitors of the influenza A M2 proton channel

Arns, Steve; Balgi, Aruna D.; Shimizu, Yoko; Pfeifer, Tom; Kumar, Nag S.; Shidmoossavee, Fahimeh S.; Sun, Sharon; Tai, Sheldon; Agafitei, Olga; Jaquith, James B.; Bourque, Élyse; Niikura, Masahiro; Roberge, Michel

doi:10.1016/j.ejmech.2016.05.008

Cited by 11 publications

(8 citation statements)

References 21 publications

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“…[15, 16] Thus the next generation of antiviral drugs with broad-spectrum antiviral activity against both drug-sensitive and drug-resistant influenza strains is clearly needed. [17, 18]…”

Section: Introductionmentioning

confidence: 99%

Design and expeditious synthesis of organosilanes as potent antivirals targeting multidrug-resistant influenza A viruses

Wang

et al. 2017

European Journal of Medicinal Chemistry

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The efficacy of current influenza vaccines and small molecule antiviral drugs is curtailed by the emerging of multidrug-resistant influenza viruses. As resistance to the only FDA-approved oral influenza antiviral, oseltamivir (Tamiflu), continues to rise, there is a clear need to develop the next-generation of antiviral drugs. Since more than 95% of current circulating influenza A viruses carry the S31N mutation in their M2 genes, the AM2-S31N mutant proton channel represents an attractive target for the development of broad-spectrum antivirals. In this study we report the design and synthesis of the first class of organosilanes that have potent antiviral activity against a panel of human clinical isolates of influenza A viruses, including viruses that are resistant to amantadine, oseltamivir, or both.

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“…[15, 16] Thus the next generation of antiviral drugs with broad-spectrum antiviral activity against both drug-sensitive and drug-resistant influenza strains is clearly needed. [17, 18]…”

Section: Introductionmentioning

confidence: 99%

Design and expeditious synthesis of organosilanes as potent antivirals targeting multidrug-resistant influenza A viruses

Wang

et al. 2017

European Journal of Medicinal Chemistry

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“…Using the M2 yeast expression, 18 novel compounds were identified [135], while another high-throughput screen identified a spirothizamenthane compound, which was used to synthesize derivatives thereof. One of the derivatives, termed compound 63, was found to inhibit the native M2, and, importantly, also S31N-and V27A-mutated M2 protein, which are amantadine-resistant mutants [136]. The M2 yeast system was used together with MDCK cells to test the efficacy and toxicity of synthesized arylsulfonamide compounds so as to elucidate the structure-activity relationship [137].…”

Section: The Yeast Saccharomyces Cerevisiae: a Powerful System For Idmentioning

confidence: 99%

Alternative Experimental Models for Studying Influenza Proteins, Host–Virus Interactions and Anti-Influenza Drugs

Chua

Engelberg

et al. 2019

Pharmaceuticals

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Ninety years after the discovery of the virus causing the influenza disease, this malady remains one of the biggest public health threats to mankind. Currently available drugs and vaccines only partially reduce deaths and hospitalizations. Some of the reasons for this disturbing situation stem from the sophistication of the viral machinery, but another reason is the lack of a complete understanding of the molecular and physiological basis of viral infections and host-pathogen interactions. Even the functions of the influenza proteins, their mechanisms of action and interaction with host proteins have not been fully revealed. These questions have traditionally been studied in mammalian animal models, mainly ferrets and mice (as well as pigs and non-human primates) and in cell lines. Although obviously relevant as models to humans, these experimental systems are very complex and are not conveniently accessible to various genetic, molecular and biochemical approaches. The fact that influenza remains an unsolved problem, in combination with the limitations of the conventional experimental models, motivated increasing attempts to use the power of other models, such as low eukaryotes, including invertebrate, and primary cell cultures. In this review, we summarized the efforts to study influenza in yeast, Drosophila, zebrafish and primary human tissue cultures and the major contributions these studies have made toward a better understanding of the disease. We feel that these models are still under-utilized and we highlight the unique potential each model has for better comprehending virus-host interactions and viral protein function.

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“…34 To further explore the possible drug target of this series of novel heteroaromatic-based benzenesulfonamide derivatives, we performed a yeast growth restoration assay. [35][36][37][38] The M2 proton channel inhibitor amantadine and neuraminidase (NA) inhibitor oseltamivir were included as reference drugs. The yeast toxicities of the heteroaromatic-based benzenesulfonamide derivatives were also evaluated to eliminate the contribution of toxic effects.…”

Section: Structure-activity Relationship (Sar) Studiesmentioning

confidence: 99%

Design and synthesis of heteroaromatic-based benzenesulfonamide derivatives as potent inhibitors of H5N1 influenza A virus

Tazeem

et al. 2019

Med. Chem. Commun.

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Novel spirothiazamenthane inhibitors of the influenza A M2 proton channel

Cited by 11 publications

References 21 publications

Design and expeditious synthesis of organosilanes as potent antivirals targeting multidrug-resistant influenza A viruses

Design and expeditious synthesis of organosilanes as potent antivirals targeting multidrug-resistant influenza A viruses

Alternative Experimental Models for Studying Influenza Proteins, Host–Virus Interactions and Anti-Influenza Drugs

Design and synthesis of heteroaromatic-based benzenesulfonamide derivatives as potent inhibitors of H5N1 influenza A virus

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