Synthesis and antiviral activity of 4,6-bis-ethylamino[1,3,5]triazine derivatives  for Flu A (H1N1) virus California/07/2009

Nowadays, control of viral diseases becomes especially relevant, considering spreading of influenza A (subtype H1N1) in this season and appearance of new coronavirus SARS-CoV-2, which caused their epidemic spreading in the world. This is why development and introduction of new highly effective antiviral drugs are a relevant direction of pharmaceutical chemistry. The aim of research is to synthesize the derivatives of (4,6-bis-amino[1,3,5]triazin-2-yl-sulphanyl)-Naryl-acetamide and to study the antiviral activity for FluA (H1N1) virus California/07/2009 at primary pharmacological screening stage. The investigated compounds – (4,6-bis-amino[1,3,5]triazin-2-yl-sulphanyl)-N-aryl-acetamide derivatives, were synthesized on the basis of 4,6-bis-ethylamino[1, 3,5]triazin-2-tiol. The antiviral activity of (4,6-bis-amino[1,3,5]triazin-2-yl-sulphanyl)-N-(2,4,6-trichlorphenyl)-acetamide against the virus FluA (H1N1) California/07/2009 was evaluated on MDCK cell culture test in vitro. It has been shown that the test substance exhibits high antiviral activity against the influenza A virus H1N1 California/ 07/2009 with effective concentration of EC50 0,6 μg/ml and the selectivity index SI > 170 (for Ribavirin SI > 160 and Amizona SI > 2,1). The data obtained substantiate the expediency of further study of derivatives of (4,6-diamino[1,3,5] triazine-2-yl-sulphanyl)-N-aryl-acetamide as potential antiviral agents.

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Amantadine Inhibits SARS-CoV-2 In Vitro

Viruses ◽

10.3390/v13040539 ◽

2021 ◽

Vol 13 (4) ◽

pp. 539

Author(s):

Klaus Fink ◽

Andreas Nitsche ◽

Markus Neumann ◽

Marica Grossegesse ◽

Karl-Heinz Eisele ◽

...

Keyword(s):

Influenza A ◽

Antiviral Agents ◽

Antiviral Drug ◽

Systemic Exposure ◽

Topical Administration ◽

Counter Measures ◽

Travel Restrictions ◽

Drug Treatments ◽

Intranasal Instillation

Since the SARS-CoV-2 pandemic started in late 2019, the search for protective vaccines and for drug treatments has become mandatory to fight the global health emergency. Travel restrictions, social distancing, and face masks are suitable counter measures, but may not bring the pandemic under control because people will inadvertently or at a certain degree of restriction severity or duration become incompliant with the regulations. Even if vaccines are approved, the need for antiviral agents against SARS-CoV-2 will persist. However, unequivocal evidence for efficacy against SARS-CoV-2 has not been demonstrated for any of the repurposed antiviral drugs so far. Amantadine was approved as an antiviral drug against influenza A, and antiviral activity against SARS-CoV-2 has been reasoned by analogy but without data. We tested the efficacy of amantadine in vitro in Vero E6 cells infected with SARS-CoV-2. Indeed, amantadine inhibited SARS-CoV-2 replication in two separate experiments with IC50 concentrations between 83 and 119 µM. Although these IC50 concentrations are above therapeutic amantadine levels after systemic administration, topical administration by inhalation or intranasal instillation may result in sufficient amantadine concentration in the airway epithelium without high systemic exposure. However, further studies in other models are needed to prove this hypothesis.

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Salidroside Protects Against Influenza A Virus-Induced Acute Lung Injury in Mice

Dose-Response ◽

10.1177/15593258211011335 ◽

2021 ◽

Vol 19 (2) ◽

pp. 155932582110113

Author(s):

Rufeng Lu ◽

Yueguo Wu ◽

Honggang Guo ◽

Zhuoyi Zhang ◽

Yuzhou He

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Influenza A Virus ◽

Influenza A ◽

H1n1 Virus ◽

Antiviral Agents ◽

Toll Like Receptor ◽

Virus Infections ◽

Toll Like Receptor 4 ◽

Inflammatory Cytokine Production

Influenza A virus infections can cause acute lung injury (ALI) in humans; thus, the identification of potent antiviral agents is urgently required. Herein, the effects of salidroside on influenza A virus-induced ALI were investigated in a murine model. BALB/c mice were intranasally inoculated with H1N1 virus and treated with salidroside. The results of this study show that salidroside treatment (30 and 60 mg/kg) significantly attenuated the H1N1 virus-induced histological alterations in the lung and inhibited inflammatory cytokine production. Salidroside also decreased the wet/dry ratio, viral titers, and Toll-like receptor 4 expression in the lungs. Therefore, salidroside may represent a potential therapeutic reagent for the treatment of influenza A virus-induced ALI.

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Antiviral activity of Ladania067, an extract from wild black currant leaves against influenza A virus in vitro and in vivo

Frontiers in Microbiology ◽

10.3389/fmicb.2014.00171 ◽

2014 ◽

Vol 5 ◽

Cited By ~ 12

Author(s):

Emanuel Haasbach ◽

Carmen Hartmayer ◽

Alice Hettler ◽

Alicja Sarnecka ◽

Ulrich Wulle ◽

...

Keyword(s):

Antiviral Activity ◽

Influenza A Virus ◽

Influenza A ◽

Black Currant

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In vitro and in vivo mechanism of immunomodulatory and antiviral activity of Edible Bird's Nest (EBN) against influenza A virus (IAV) infection

Journal of Ethnopharmacology ◽

10.1016/j.jep.2016.03.020 ◽

2016 ◽

Vol 185 ◽

pp. 327-340 ◽

Cited By ~ 15

Author(s):

Amin Haghani ◽

Parvaneh Mehrbod ◽

Nikoo Safi ◽

Nur Ain Aminuddin ◽

Azadeh Bahadoran ◽

...

Keyword(s):

Antiviral Activity ◽

Influenza A Virus ◽

Influenza A ◽

Edible Bird’S Nest

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Antiviral Activity of Benzoic Acid Derivative NC-5 Against Influenza A Virus and Its Neuraminidase Inhibition

International Journal of Molecular Sciences ◽

10.3390/ijms20246261 ◽

2019 ◽

Vol 20 (24) ◽

pp. 6261

Author(s):

Min Guo ◽

Jiawei Ni ◽

Jie Yu ◽

Jing Jin ◽

Lingman Ma ◽

...

Keyword(s):

Antiviral Activity ◽

Benzoic Acid ◽

Influenza A Virus ◽

Influenza A ◽

Matrix Protein ◽

Influenza Viruses ◽

Drug Candidate ◽

Dependent Manner ◽

Drug Resistant

The currently available drugs against influenza A virus primarily target neuraminidase (NA) or the matrix protein 2 (M2) ion channel. The emergence of drug-resistant viruses requires the development of new antiviral chemicals. Our study applied a cell-based approach to evaluate the antiviral activity of a series of newly synthesized benzoic acid derivatives, and 4-(2,2-Bis(hydroxymethyl)-5-oxopyrrolidin-l-yl)-3-(5-cyclohexyl-4H-1,2,4-triazol-3-yl)amino). benzoic acid, termed NC-5, was found to possess antiviral activity. NC-5 inhibited influenza A viruses A/FM/1/47 (H1N1), A/Beijing/32/92 (H3N2) and oseltamivir-resistant mutant A/FM/1/47-H275Y (H1N1-H275Y) in a dose-dependent manner. The 50% effective concentrations (EC50) for H1N1 and H1N1-H275Y were 33.6 μM and 32.8 μM, respectively, which showed that NC-5 had a great advantage over oseltamivir in drug-resistant virus infections. The 50% cytotoxic concentration (CC50) of NC-5 was greater than 640 μM. Orally administered NC-5 protected mice infected with H1N1 and H1N1-H275Y, conferring 80% and 60% survival at 100 mg/kg/d, reducing body weight loss, and alleviating virus-induced lung injury. NC-5 could suppress NP and M1 protein expression levels during the late stages of viral biosynthesis and inhibit NA activity, which may influence virus release. Our study proved that NC-5 has potent anti-influenza activity in vivo and in vitro, meaning that it could be regarded as a promising drug candidate to treat infection with influenza viruses, including oseltamivir-resistant viruses.

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#Nitrosocarbonyls 1: Antiviral Activity ofN-(4-Hydroxycyclohex-2-en-1-yl)quinoline-2-carboxamide against the Influenza A Virus H1N1

The Scientific World JOURNAL ◽

10.1155/2014/472373 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Dalya Al-Saad ◽

Misal Giuseppe Memeo ◽

Paolo Quadrelli

Keyword(s):

Influenza Virus ◽

Antiviral Activity ◽

Small Molecules ◽

Influenza A ◽

Nucleoside Analogues ◽

Virus H1n1 ◽

Antiviral Activities ◽

Synthetic Approaches ◽

Carbocyclic Nucleoside

Influenza virus flu A H1N1 still remains a target for its inhibition with small molecules. Fleeting nitrosocarbonyl intermediates are at work in a short-cut synthesis of carbocyclic nucleoside analogues. The strategy of the synthetic approaches is presented along with thein vitroantiviral tests. The nucleoside derivatives were tested for their inhibitory activity against a variety of viruses. Promising antiviral activities were found for specific compounds in the case of flu A H1N1.

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