An oligothiophene compound neutralized influenza A viruses by interfering with hemagglutinin

Shen, Xintian; Zhu, Zhibo; Ding, Yi; Wu, Wenjiao; Yang, Jie; Liu, Shuwen

doi:10.1016/j.bbamem.2017.12.006

Cited by 6 publications

(6 citation statements)

References 21 publications

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“…Several studies reported the viricidal potentialities of different molecules through the inhibition of the hemagglutinin protein [ 118 , 119 , 120 ]. Accordingly, we investigated the abilities of β -sitosterol and β -sitosterol- O -glucoside against such protein.…”

Section: Discussionmentioning

confidence: 99%

Phytoestrogen β-Sitosterol Exhibits Potent In Vitro Antiviral Activity against Influenza A Viruses

et al. 2023

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Influenza is a contagious infection in humans that is caused frequently by low pathogenic seasonal influenza viruses and occasionally by pathogenic avian influenza viruses (AIV) of H5, H7, and H9 subtypes. Recently, the clinical sector in poultry and humans has been confronted with many challenges, including the limited number of antiviral drugs and the rapid evolution of drug-resistant variants. Herein, the anti-influenza activities of various plant-derived phytochemicals were investigated against highly pathogenic avian influenza A/H5N1 virus (HPAIV H5N1) and seasonal low pathogenic human influenza A/H1N1 virus (LPHIV H1N1). Out of the 22 tested phytochemicals, the steroid compounds β-sitosterol and β-sitosterol-O-glucoside have very potent activity against the predefined influenza A viruses (IAV). Both steroids could induce such activity by affecting multiple stages during IAV replication cycles, including viral adsorption and replication with a major and significant impact on the virus directly in a cell-free status “viricidal effect”. On a molecular level, several molecular docking studies suggested that β-sitosterol and β-sitosterol-O-glucoside exhibited viricidal effects through blocking active binding sites of the hemagglutinin surface protein, as well as showing inhibitory effects against replication through the binding with influenza neuraminidase activity and blocking the active sites of the M2 proton channel activity. The phytoestrogen β-sitosterol has structural similarity with the active form of the female sex hormone estradiol, and this similarity is likely one of the molecular determinants that enables the phytoestrogen β-sitosterol and its derivative to control IAV infection in vitro. This promising anti-influenza activity of β-sitosterol and its O-glycoside derivative, according to both in vitro and cheminformatics studies, recommend both phytochemicals for further studies going through preclinical and clinical phases as efficient anti-influenza drug candidates.

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Section: Discussionmentioning

confidence: 99%

Phytoestrogen β-Sitosterol Exhibits Potent In Vitro Antiviral Activity against Influenza A Viruses

et al. 2023

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“…Neuraminidase inhibition assay was performed to investigate the influence of a test compound on the release of newly produced viral particles, as described previously ( Shen et al, 2018 ). Briefly, 15 μL of A/Puerto Rico/8/1934(H1N1) virus solution were mixed with 5 μL of a test compound at graded concentrations in wells of a 96-well black plate, followed by incubation at 37°C for 30 min.…”

Section: Methodsmentioning

confidence: 99%

“…The HI assay was performed to measure the inhibitory activity of a test compound on attachment of an influenza virus to red blood cells (RBC) through the interaction between HA on virus and receptor on RBC, as described previously ( Shen et al, 2018 ). A/Shanghai/37T 2009(H1N1) virus or H7N9 pseudovirus at the concentration of 4 HA units were prepared.…”

Section: Methodsmentioning

confidence: 99%

The Antihistamine Drugs Carbinoxamine Maleate and Chlorpheniramine Maleate Exhibit Potent Antiviral Activity Against a Broad Spectrum of Influenza Viruses

Xia

et al. 2018

Front. Microbiol.

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Influenza A viruses (IAV) comprise some of the most common infectious pathogens in humans, and they cause significant mortality and morbidity in immunocompromised people as well as children and the elderly. After screening an FDA-approved drug library containing 1280 compounds by cytopathic effect (CPE) reduction assay using the Cell Counting Kit-8, we found two antihistamines, carbinoxamine maleate (CAM) and S-(+)-chlorpheniramine maleate (SCM) with potent antiviral activity against A/Shanghai/4664T/2013(H7N9) infection with IC50 (half-maximal inhibitory concentration) of 3.56 and 11.84 μM, respectively. Further studies showed that CAM and SCM could also inhibit infection by other influenza A viruses, including A/Shanghai/37T/2009(H1N1), A/Puerto Rico/8/1934(H1N1), A/Guizhou/54/1989(H3N2), and one influenza B virus, B/Shanghai/2017(BY). Mice were challenged intranasally with A/H7N9/4664T/2013 (H7N9) virus and intraperitoneally injected with CAM (10 mg/kg per day) or SCM (1 mg/kg per day) for 5 days. CAM or SCM (10 mg/kg per day) were fully protected against challenge with A/Shanghai/4664T/2013(H7N9). The results from mechanistic studies indicate that both could inhibit influenza virus infection by blocking viral entry into the target cell, the early stage of virus life cycle. However, CAM and SCM neither blocked virus attachment, characteristic of HA activity, nor virus release, characteristic of NA activity. Such data suggest that these two compounds may interfere with the endocytosis process. Thus, we have identified two FDA-approved antihistamine drugs, CAM and SCM, which can be repurposed for inhibiting infection by divergent influenza A strains and one influenza B strain with potential to be used for treatment and prevention of influenza virus infection.

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“…Similar studies [36] are of greater interest from the perspective of the rational design of a universal vaccine. However, for drug development, in the case of HA, binding sites located in the conservative region of the stem part of the protein are most often considered [37][38][39][40].…”

Section: Binding Sites Of Small Molecules In Hamentioning

confidence: 99%

Molecular Modeling of Viral Type I Fusion Proteins: Inhibitors of Influenza Virus Hemagglutinin and the Spike Protein of Coronavirus

Borisevich

Zarubaev

Щербаков

et al. 2023

Viruses

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The fusion of viral and cell membranes is one of the basic processes in the life cycles of viruses. A number of enveloped viruses confer fusion of the viral envelope and the cell membrane using surface viral fusion proteins. Their conformational rearrangements lead to the unification of lipid bilayers of cell membranes and viral envelopes and the formation of fusion pores through which the viral genome enters the cytoplasm of the cell. A deep understanding of all the stages of conformational transitions preceding the fusion of viral and cell membranes is necessary for the development of specific inhibitors of viral reproduction. This review systematizes knowledge about the results of molecular modeling aimed at finding and explaining the mechanisms of antiviral activity of entry inhibitors. The first section of this review describes types of viral fusion proteins and is followed by a comparison of the structural features of class I fusion proteins, namely influenza virus hemagglutinin and the S-protein of the human coronavirus.

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An oligothiophene compound neutralized influenza A viruses by interfering with hemagglutinin

Abstract: Oligothiophene compound 4sc is a novel selective virucide of influenza virus, which blocks entry by interfering viral hemagglutinin. Due to promising safety profile and stable virucidal effect at 4°C, 4sc may be useful in disinfecting H5N1 and H1N1 influenza virus.

Cited by 6 publications

References 21 publications

Phytoestrogen β-Sitosterol Exhibits Potent In Vitro Antiviral Activity against Influenza A Viruses

Phytoestrogen β-Sitosterol Exhibits Potent In Vitro Antiviral Activity against Influenza A Viruses

The Antihistamine Drugs Carbinoxamine Maleate and Chlorpheniramine Maleate Exhibit Potent Antiviral Activity Against a Broad Spectrum of Influenza Viruses

Molecular Modeling of Viral Type I Fusion Proteins: Inhibitors of Influenza Virus Hemagglutinin and the Spike Protein of Coronavirus

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