Broad range of inhibiting action of novel camphor-based compound with anti-hemagglutinin activity against influenza viruses in vitro and in vivo.
Abstract
Influenza virus continues to remain one of the leading human respiratory pathogens causing significant morbidity and mortality around the globe. Due to short-term life cycle and high rate of mutations influenza virus is able to rapidly develop resistance to clinically available antivirals. This makes necessary the search and development of new drugs with different targets and mechanisms of activity. Here we report anti-influenza activity of camphor derivative 1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene-aminoethanol (camphecene). In in vitro experiments it inhibited influenza viruses A(H1, H1pdm0...
Source: Antiviral Research - June 10, 2015 Category: Virology Authors: Zarubaev VV, Garshinina AV, Tretiak TS, Fedorova VA, Shtro AA, Sokolova AS, Yarovaya OI, Salakhutdinov NF Tags: Antiviral Res Source Type: research
Synthesis, characterization and interaction with bovine serum albumin of cyclometallated Pd(II) complexes containing arylimine and salicylaldimine co-ligands
Publication date: 15 August 2015 Source:Journal of Organometallic Chemistry, Volume 791 Author(s): Xu-Dong Jin , Yajing Yang , Yuchun Jiang , Xiang Han , Xiaowen Wan , Daliang Liu , Xi-Ming Song , Xiaohong Chang Cyclometallated Pd(II) complexes containing arylimine and salicylaldimine co-ligands were synthesized by the reactions of cyclopalladated chloro dimers [Pd{(4-R)C6H3CHN–C6H3-2,6-i-Pr2}(μ-Cl)]2 (R = H; OMe) with salen-based ligands derived from rimantadine. The complexes were characterized by FTIR, NMR spectroscopy, elemental analysis and X-ray crystallography. Interaction of cyclometallated Pd(II) ...
Source: Journal of Organometallic Chemistry - June 2, 2015 Category: Chemistry Source Type: research
Steered molecular dynamics approach for promising drugs for influenza A virus targeting M2 channel proteins.
Abstract
We have used steered molecular dynamics simulation to investigate the molecular interactions between four M2 inhibitors (amantadine, rimantadine, and two other amantadine derivatives) and the M2 protein channels of influenza A virus H5N1, including the wild type (WT) and three previously identified drug-resistant variants (G34A, S31N, and V27A). The binding free energies between these four inhibitors and the M2 channel of the WT and the three mutants were also determined by use of the molecular mechanics-Poisson-Boltzmann surface area method. Our study provides important insight into binding affin...
Source: European Biophysics Journal : EBJ - June 2, 2015 Category: Physics Authors: Nguyen H, Le L Tags: Eur Biophys J Source Type: research
Transverse relaxation dispersion of the p7 membrane channel from hepatitis C virus reveals conformational breathing.
Abstract
The p7 membrane protein encoded by hepatitis C virus (HCV) assembles into a homo-hexamer that selectively conducts cations. An earlier solution NMR structure of the hexameric complex revealed a funnel-like architecture and suggests that a ring of conserved asparagines near the narrow end of the funnel are important for cation interaction. NMR based drug-binding experiments also suggest that rimantadine can allosterically inhibit ion conduction via a molecular wedge mechanism. These results suggest the presence of dilation and contraction of the funnel tip that are important for channel activity an...
Source: Journal of Bimolecular NMR - February 28, 2015 Category: Biomedical Science Authors: Dev J, Brüschweiler S, Ouyang B, Chou JJ Tags: J Biomol NMR Source Type: research
Inhibitors Targeting the Influenza Virus Hemagglutinin.
Abstract
The annual flu season causes thousands of deaths and millions of hospitalizations, which pose a great burden to global health and economy. Moreover, a flu pandemic arising from re-assortment viruses, such as H5N1 and H1N1, raises even greater concern due to the lack of effective vaccines at the initial stage of flu outbreak. The influenza virus is the causative agent of flu infection. Currently there are four drugs in use to combat influenza infection. Amantadine and rimantadine are M2 proton channel blockers that inhibit virus un-coating; oseltamivir and zanamivir are neuraminidase (NA) inhibitor...
Source: Current Medicinal Chemistry - February 27, 2015 Category: Chemistry Authors: Li F, Ma C, Wang J Tags: Curr Med Chem Source Type: research
Synthesis and preliminary antiviral activities of piperidine‐substituted purines against HIV and influenza A/H1N1 infections
This article is protected by copyright. All rights reserved.
SAR of N2‐(1‐arylpiperidin‐4‐yl)‐N6‐(2,4,6‐trimethylphenyl)‐9H‐purine‐2,6‐diamine and its antiviral activity against HIV and influenza A/H1N1 infections. (Source: Chemical Biology and Drug Design)
Source: Chemical Biology and Drug Design - January 20, 2015 Category: Biology Authors: Dongwei Kang, Zengjun Fang, Boshi Huang, Lingzi Zhang, Huiqing Liu, Christophe Pannecouque, Lieve Naesens, Erik De Clercq, Peng Zhan, Xinyong Liu Tags: Research Article Source Type: research
Amantadine and rimantadine for influenza A in children and the elderly.
CONCLUSIONS: The quality of the evidence combined with a lack of knowledge about the safety of amantadine and the limited benefits of rimantadine, do not indicate that amantadine and rimantadine compared to control (placebo or paracetamol) could be useful in preventing, treating and shortening the duration of influenza A in children and the elderly.
PMID: 25415374 [PubMed - as supplied by publisher] (Source: Cochrane Database of Systematic Reviews)
Source: Cochrane Database of Systematic Reviews - November 21, 2014 Category: Journals (General) Authors: Alves Galvão MG, Rocha Crispino Santos MA, Alves da Cunha AJ Tags: Cochrane Database Syst Rev Source Type: research
Drug inhibition and proton conduction mechanisms of the influenza a m2 proton channel.
Authors: Gu R, Liu LA, Wei D
Abstract
The influenza A virus matrix protein 2 (M2 protein) is a pH-regulated proton channel embedded in the viral membrane. Inhibition of the M2 proton channel has been used to treat influenza infections for decades due to the crucial role of this protein in viral infection and replication. However, the widely-used M2 inhibitors, amantadine and rimantadine, have gradually lost their efficiencies because of naturally-occurring drug resistant mutations. Therefore, investigation of the structure and function of the M2 proton channel will not only increase our understanding of th...
Source: Advances in Experimental Medicine and Biology - November 15, 2014 Category: Research Tags: Adv Exp Med Biol Source Type: research
Docking assay of small molecule antivirals to p7 of HCV.
Abstract
Protein p7 of HCV is a 63 amino acid channel forming membrane protein essential for the progression of viral infection. With this momentousness, p7 emerges as an important target for antiviral therapy. A series of small molecule drugs, such as amantadine, rimantadine, amiloride, hexamethylene amiloride, NN-DNJ and BIT225 have been found to affect the channel activity. These compounds are docked against monomeric and hexameric structures of p7 taken at various time steps from a molecular dynamics simulation of the protein embedded in a hydrated lipid bilayer. The energetics of binding identifies th...
Source: Computational Biology and Chemistry - November 13, 2014 Category: Bioinformatics Authors: Bichmann L, Wang YT, Fischer WB Tags: Comput Biol Chem Source Type: research
Viral M2 Ion Channel Protein: A Promising Target for Anti-influenza Drug Discovery.
Abstract
Influenza virus is an important RNA virus causing pandemics (Spanish Flu (1918), Asian Flu (1957), Hong Kong Flu (1968) and Swine Flu (2009)) over the last decades. Due to the spontaneous mutations of these viral proteins, currently available antiviral and anti-influenza drugs quickly develop resistance. To account this, only limited antiinfluenza drugs have been approved for the therapeutic use. These include amantadine and rimantadine (M2 proton channel blockers), zanamivir, oseltamivir and peramivir (neuraminidase inhibitors), favipravir (polymerase inhibitor) and laninamivir. This review provi...
Source: Mini Reviews in Medicinal Chemistry - October 28, 2014 Category: Chemistry Authors: Moorthy NS, Poongavanam V, Pratheepa V Tags: Mini Rev Med Chem Source Type: research
Antivirals - current trends in fighting influenza.
Abstract
Influenza virus infection is a major source of morbidity and mortality worldwide. Due to the variable effectiveness of existing vaccines, especially in the early stages of an epidemic, antiviral drugs represent the first line of defense against the virus. Currently, there are two major classes of anti-influenza drugs approved by the FDA for clinical use: M2 protein inhibitors (amantadine and rimantadine) and neuraminidase inhibitors (zanamivir and oseltamivir). However, increasing resistance to these available influenza antivirals among circulating influenza viruses highlights the need to develop ...
Source: Acta Biochim Pol - September 1, 2014 Category: Biochemistry Authors: Król E, Rychłowska M, Szewczyk B Tags: Acta Biochim Pol Source Type: research
Research/Review: Structure and Linkage Disequilibrium Analysis of Adamantane Resistant Mutations in Influenza Virus M2 Proton Channel.
Abstract
The M2 proton channel is translated by the M gene segment of influenza viruses, and has been adopted as an attractive target for influenza A viruses, on which a series of adamantane-based drugs act. However, recently epidemic influenza viruses have strong resistant effects against the adamantane-based drugs. In this paper, we combined evolutionary analyses, linkage disequilibrium as well as molecular dynamics simulations to explore the drug resistance of the M2 proton channel, with an aim of providing an in-depth understanding of the resistant mechanism for adamantane-based drugs. We collected 274...
Source: Current Drug Metabolism - June 5, 2014 Category: Drugs & Pharmacology Authors: Yu Y, Li X, Hao P, Wang JF, Chou KC Tags: Curr Drug Metab Source Type: research
Synthesis, characterization, and crystal structure of three cobalt(II) complexes with Schiff bases derived from rimantadine
(Source: Journal of Coordination Chemistry)
Source: Journal of Coordination Chemistry - March 10, 2014 Category: Chemistry Authors: Xu, ChongLiu, Xiao-ChenJin, Xu-DongYang, QiHan, Guang-ChaoGang, Yu-ChenHu, Hai-Hong Source Type: research
Camphor-based symmetric diimines as inhibitors of influenza virus reproduction.
Abstract
Influenza is a continuing world-wide public health problem that causes significant morbidity and mortality during seasonal epidemics and sporadic pandemics. The purpose of the study was synthesis and investigation of antiviral activity of camphor-based symmetric diimines and diamines. A set of C2-symmetric nitrogen-containing camphor derivatives have been synthesized. The antiviral activity of these compounds was studied against rimantadine- and amantadine-resistant influenza virus A/California/7/09 (H1N1)pdm09 in MDCK cells. The highest efficacy in virus inhibiting was shown for compounds 2a-e wi...
Source: Bioorganic and Medicinal Chemistry - March 1, 2014 Category: Chemistry Authors: Sokolova AS, Yarovaya CO, Korchagina DV, Zarubaev VV, Tretiak TS, Anfimov PM, Kiselev OI, Salakhutdinov NF Tags: Bioorg Med Chem Source Type: research
Antiviral Susceptibility of Highly Pathogenic Avian Influenza A(H5N1) Viruses Isolated from Poultry, Vietnam, 2009-2011.
Abstract
We assessed drug susceptibilities of 125 avian influenza A(H5N1) viruses isolated from poultry in Vietnam during 2009-2011. Of 25 clade 1.1 viruses, all possessed a marker of resistance to M2 blockers amantadine and rimantadine; 24 were inhibited by neuraminidase inhibitors. One clade 1.1 virus contained the R430W neuraminidase gene and reduced inhibition by oseltamivir, zanamivir, and laninamivir 12-, 73-, and 29-fold, respectively. Three of 30 clade 2.3.4 viruses contained a I223T mutation and showed 7-fold reduced inhibition by oseltamivir. One of 70 clade 2.3.2.1 viruses had the H275Y marker o...
Source: Emerging Infectious Diseases - November 30, 2013 Category: Infectious Diseases Authors: Nguyen HT, Nguyen T, Mishin VP, Sleeman K, Balish A, Jones J, Creanga A, Marjuki H, Uyeki TM, Nguyen DH, Nguyen DT, Do HT, Klimov AI, Davis CT, Gubareva LV Tags: Emerg Infect Dis Source Type: research
