» Articles » PMID: 34583607

Anti-influenza A Virus Activity and Structure-activity Relationship of a Series of Nitrobenzoxadiazole Derivatives

Overview
Specialty Biochemistry
Date 2021 Sep 29
PMID 34583607
Citations 2
Authors
Affiliations
Soon will be listed here.
Abstract

Influenza viruses represent a major threat to human health and are responsible for seasonal epidemics, along with pandemics. Currently, few therapeutic options are available, with most drugs being at risk of the insurgence of resistant strains. Hence, novel approaches targeting less explored pathways are urgently needed. In this work, we assayed a library of nitrobenzoxadiazole derivatives against the influenza virus A/Puerto Rico/8/34 H1N1 (PR8) strain. We identified three promising 4-thioether substituted nitrobenzoxadiazoles (, , and ) that were able to inhibit viral replication at low micromolar concentrations in two different infected cell lines using a haemagglutination assay. We further assessed these molecules using an In-Cell Western assay, which confirmed their potency in the low micromolar range. Among the three molecules, and displayed the most favourable profile of activity and selectivity and were selected as hit compounds for future optimisation studies.

Citing Articles

ECHOPvir: A Mixture of Echinacea and Hop Extracts Endowed with Cytoprotective, Immunomodulatory and Antiviral Properties.

Percaccio E, De Angelis M, Acquaviva A, Nicotra G, Ferrante C, Mazzanti G Nutrients. 2023; 15(20).

PMID: 37892456 PMC: 10609862. DOI: 10.3390/nu15204380.


Screening and characterization of inhibitory vNAR targeting nanodisc-assembled influenza M2 proteins.

Yu C, Ding W, Zhu L, Zhou Y, Dong Y, Li L iScience. 2022; 26(1):105736.

PMID: 36570769 PMC: 9771723. DOI: 10.1016/j.isci.2022.105736.

References
1.
Marcocci M, Amatore D, Villa S, Casciaro B, Aimola P, Franci G . The Amphibian Antimicrobial Peptide Temporin B Inhibits Herpes Simplex Virus 1 Infection. Antimicrob Agents Chemother. 2018; 62(5). PMC: 5923125. DOI: 10.1128/AAC.02367-17. View

2.
Rotili D, De Luca A, Tarantino D, Pezzola S, Forgione M, Morozzo Della Rocca B . Synthesis and structure--activity relationship of new cytotoxic agents targeting human glutathione-S-transferases. Eur J Med Chem. 2014; 89:156-71. DOI: 10.1016/j.ejmech.2014.10.033. View

3.
Kessler U, Castagnolo D, Pagano M, Deodato D, Bernardini M, Pilger B . Discovery and synthesis of novel benzofurazan derivatives as inhibitors of influenza A virus. Bioorg Med Chem Lett. 2013; 23(20):5575-7. DOI: 10.1016/j.bmcl.2013.08.048. View

4.
Tumpey T, Belser J . Resurrected pandemic influenza viruses. Annu Rev Microbiol. 2009; 63:79-98. DOI: 10.1146/annurev.micro.091208.073359. View

5.
Das K . Antivirals targeting influenza A virus. J Med Chem. 2012; 55(14):6263-77. DOI: 10.1021/jm300455c. View