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A₃- and A₂B-nitrocorroles: synthesis and antiviral activity evaluation against human cytomegalovirus infection.

ABSTRACT: Human cytomegalovirus (hCMV) is responsible for several pathologies impacting immunocompromised patients and can trigger life-threatening infection. Several antivirals are available and are used in the clinic, but hCMV resistant strains have appeared and patients have encountered therapeutic failure. Hence, there is a constant need for new best in class or first in class antiviral molecules. We have previously shown that nitrocorroles could be used as a potent anti-hCMV agent without acute toxicity in mice. They therefore represent an excellent platform to perform structure-activity relationship (SAR) studies and to increase efficiency or reduce toxicity. We have generated original A₂B- and A₃-substituted nitrocorroles and have discovered optimized compounds with selectivity indices above 200. These compounds are easily synthesized in only one to two-step reactions; they are up-scalable and cost efficient. They are therefore excellent candidates for hCMV therapies and they pave the way for a new generation of molecules.

SUBMITTER: Bucher L

PROVIDER: S-EPMC7605276 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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A<sub>3</sub>- and A<sub>2</sub>B-nitrocorroles: synthesis and antiviral activity evaluation against human cytomegalovirus infection.

Bucher Léo L Kappler-Gratias Sandrine S Desbois Nicolas N Bystricky Kerstin K Gallardo Franck F Gros Claude P CP

RSC medicinal chemistry 20200519 7

Human cytomegalovirus (hCMV) is responsible for several pathologies impacting immunocompromised patients and can trigger life-threatening infection. Several antivirals are available and are used in the clinic, but hCMV resistant strains have appeared and patients have encountered therapeutic failure. Hence, there is a constant need for new best in class or first in class antiviral molecules. We have previously shown that nitrocorroles could be used as a potent anti-hCMV agent without acute toxic ...[more]

PMID: 33479674

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Project description:BackgroundThe antiviral properties of metal nanoparticles against various viruses, including those resistant to drugs, are currently a subject of intensive research. Recently, the green synthesis of nanoparticles and their anti-viral function have attracted a lot of attention. Previous studies have shown promising results in the use of Arabic gum for the green synthesis of nanoparticles with strong antiviral properties. In this study we aimed to investigate the antiviral effects of MnO2 nanoparticles (MnO2-NPs) synthesized using Arabic gum, particularly against the influenza virus.MethodsArabic gum was used as a natural polymer to extract and synthesize MnO2-NPs using a green chemistry approach. The synthesized MnO2-NPs were characterized using SEM and TEM. To evaluate virus titration, cytotoxicity, and antiviral activity, TCID50, MTT, and Hemagglutination assay (HA) were performed, respectively. Molecular docking studies were also performed to investigate the potential antiviral activity of the synthesized MnO2-NPs against the influenza virus. The molecular docking was carried out using AutoDock Vina software followed by an analysis with VMD software to investigate the interaction between Arabic gum and the hemagglutinin protein.ResultsSimultaneous combination treatment with the green-synthesized MnO2-NPs resulted in a 3.5 log HA decrement and 69.7% cellular protection, which demonstrated the most significant difference in cellular protection compared to the virus control group (p-value < 0.01). The docking results showed that binding affinities were between - 3.3 and - 5.8 kcal/mole relating with the interaction between target with MnO2 and beta-D-galactopyranuronic acid, respectively.ConclusionThe results of the study indicated that the MnO2-NPs synthesized with Arabic gum had significant antiviral effects against the influenza virus, highlighting their potential as a natural and effective treatment for inhibition of respiratory infections.

Dataset Information

A₃- and A₂B-nitrocorroles: synthesis and antiviral activity evaluation against human cytomegalovirus infection.

Publications

A<sub>3</sub>- and A<sub>2</sub>B-nitrocorroles: synthesis and antiviral activity evaluation against human cytomegalovirus infection.

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A3- and A2B-nitrocorroles: synthesis and antiviral activity evaluation against human cytomegalovirus infection.

Publications

A<sub>3</sub>- and A<sub>2</sub>B-nitrocorroles: synthesis and antiviral activity evaluation against human cytomegalovirus infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

A₃- and A₂B-nitrocorroles: synthesis and antiviral activity evaluation against human cytomegalovirus infection.