Influenza virus in vitro

Amino- and hydrazino-quinazolines exhibited antibacterial ac-tivity and a patent claim on the in vitro action of 2,4-diamino-quinazolines was rnade. The preparation of thiopegan derivatives as potential antimalarials and antibacterials deserves mention. Complete inhibition of influenza virus in vitro but not in vivo was shown by. 6,8-dichloro-2,4-dihydroxyquinazoline and other cyclic ureas. Activity against trachoma virus was also displayed by several 2-trichloromethylquinazolines. ... 

Zakay-Rones, Zichria, Ph.D., Varsano, Noemi, M.Sc., Zlotnik, Moshe, M.D., Manor, Orly, Ph D., Regev, Liora, Schlesinger, Miriam and Mumcuoglu, Madeleine, Ph.D., "Inhibition of Several Strains of Influenza Virus in Vitro and Reduction of Symptoms by an Elderberry Extract, The Journal of Alternative and Complementary Medicine, Volume 1, Number 4, 1995, pages 361369. 

Thomas GP, Forsyth M, Penn CR, McCauley JW. Inhibition of growth of influenza virus in vitro by... 

The discovery of Zanamivir as a potent and selective inhibitor of influenza virus sialidase prompted several researchers to investigate the synthesis and structure-activity relationship studies of Neu5Ac2en-based compounds as potential sialidase inhibitors. Exploration of these SAR studies were undertaken to optimize inhibitory activity and to improve the physicochemical properties of the sialic acid-based influenza virus sialidase inhibitor. A few in vitro assays are commonly employed to measure the effectiveness of influenza virus sialidase inhibitors. The first involves a fluorometric assay that measures release of a synthetic fluorophore following its cleavage from Neu5Ac by sialidase. Dye-uptake assay, such as the Neutral Red uptake assay, measures the uptake of a vital stain, Neutral Red in cell culture. The process requires intact membranes and active metabolism in the cell, and is expressed as percent protective rate against virus infection. The plaque-reduction assay is used to measure sialidase inhibition indirectly in cell culture, and provides some measure of the inhibitor s effect on the viability of the influenza virus. In vitro and in vivo systems for analysis of inhibitors of influenza virus enzymes have been reviewed.71... 

Yang et al. (2005) stndied the anti-influenza virus activities of the volatile oil from the roots of the Asclepiadaceae Cynanchum stauntonii and found that the volatile oil caused an antiviral effect against influenza virus in vitro and also in in vivo experiments and was able to prevent the number of deaths induced by the virus in a dose-dependent manner. 

Zakay-Rones Z, Varsano N, Zlotnik M, Manor O, Regev L, Schlesinger M, et al (1995) Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama. J. Altem Complement Med 1 361 - 369. 

Pyrazofurin (PF, 3-3 D-ribofuranosyl-4-hydroxypyrazol-5--carboxamide, Eli Lilly Compound 47599, formerly called Pyrazomycin) is a carbon-linked nucleoside (Fig. 1) isolated from the broth filtrates of a strain of Streptomyces candidus (1). PF exhibits antiviral activity against several viruses, including herpes, rhino, measles, and influenza viruses in vitro (1), vaccinia... 

Honeysuckle flower is active against various bacteria (Staphylococcus aureus. Salmonella typhi, Mycobacterium tuberculosis, dysentery bacilli, etc.) and viruses (e.g., HIV and influenza viruses) in vitro and/or in vivo also active against dermatophjites but to a less extent. It has anti-inflammatory effects on several experimental inflammation models. Other effects include strengthening body... 

Influenza virus resistant to oseltamivir has not been found in naturally acquired isolates but has been isolated from influenza patients who have undergone treatment with this drug. These resistant strains contain mutations in the active site of neuraminidase and are generally less virulent and infective than nonresistant virus. In vitro passage of influenza virus in the presence of oseltamivir carboxylate can produce mutations in hemagglutinin that decrease the overall dependence of viral replication on neuraminidase however, the clinical relevance of this resistance mechanism is unknown. 

Intravenous ribavirin decreases mortality in patients with Lassa fever and other viral hemorrhagic fevers if started early. High concentrations inhibit West Nile virus in vitro, but clinical data are lacking. Clinical benefit has been reported in cases of severe measles pneumonitis and certain encephalitides, and continuous infusion of ribavirin has decreased virus shedding in several patients with severe lower respiratory tract influenza or parainfluenza infections. At steady state, cerebrospinal fluid levels are about 70% of those in plasma. 

Rimantadine hydrochloride, an alpha-methyl derivative of amantadine (alpha-methyl-l-adamantane methylamine hydrochloride), is more active than amantadine against influenza A viruses in vitro and in laboratory animals. It is an alternative to amantadine for the prevention and treatment of influenza A virus infections in adults and for the prevention of influenza in children. Adverse effects have been considered to be less common with rimantadine (SEDA-8, 143), and it is generally tolerated better than amantadine, because it causes fewer nervous system adverse effects (1). Unfortunately, rimantadine is more costly, which has led many institutions to develop influenza treatment guidelines. Both drugs work by blocking the M2 ion channel, which is needed to affect a pH change that helps to initiate viral uncoating. 

Barbituric acid only partially inhibited RNA or protein synthesis in tissue cultures of embryonic chick skin at 833 pg/ml, whereas puromycin was inhibitory at 1 7-333 pg/ml [131]. Several urea derivatives, including barbituric acid, completely inhibited influenza PR-8 virus in vitro, but were without effect in vivo in chick embryos [132]. 

Several aromatic derivatives of guanidine (LVI-LVIII) as their sulphates were active against influenza PR8 and Sendai virus in vitro. Tlie minimum inhibitory concentrations ranged from 35-125 pg/ml but again no toxidties were given [232]. 

Previous studies demonstrated the antiviral activity of ascorbate against a broad spectrum of RNA and DNA viruses in vitro (1-4) and in vivo (5, 6). It has been claimed that ascorbate inhibited the activation of a latent human retrovirus (human T-cell leukemia virus 1) induced by 5-iodo-2 -deoxyuridine and JV-methyl-A/ -nitro-A-nitrosoguanidine (7). However, it was not established whether ascorbate exerted a virus-specific effect or interacted directly with the activating substances. In addition, the effects of ascorbate on acute infection by human retroviruses have not been determined. In vivo, oral, and intravenous administration of ascorbate is said to have produced clinical improvements in patients afflicted with influenza, hepatitis, and herpes virus infections, including infectious mononucleosis (5, 6). Clinical improvement was claimed in AIDS patients who voluntarily ingested high doses of ascorbic acid (8). 

Nostoflan Nostoc flagelliforme (cyanobacterium) HSV-1, HSV-2, human cytomegalovirus and influenza A virus, in-vitro [87]... 

Woods, JA4., Bethell, R.C., Coates, J.A.V., Healy, N., Hiscox, S.A., Pearson, BA., Ryan, DA4., Ticehurst, J., Tilling, J., Walcott, S.M., and Penn, CJl. (1993) 4-Guanidino-2,4-dideoxy-23-dehydro-Af-acetylneuraminic acid is a highly effective inhibitor both of the sialidase (neuraminidase) and of growth of a wide range of influenza A and influenza B viruses in vitro. Antimicrobial... 

A root extract had a marked antiviral effect against the RNA viruses human rhinovirus, respiratory syncytial virus, and influenza A virus in vitro. DNA viruses were not affected by the same extract. ... 

Wang, Z., Chai, W, Burwinkel, M., et al. (2013b) Inhibitory influence of Enterococcus faecium on the propagation of swine influenza A virus in vitro. PLoS One 8, e53043. 

Neu5Ac2en 4, a micromolar inhibitor of influenza virus sialidase 4 x 10 M (A/N2)] (Holzer et al. 1993), was first identified as a very good inhibitor in the late 1960s (Meindl and Tuppy 1969). A series of C-5 modified Neu5Ac2en derivatives provided the first improved in vitro inhibitors compared with the parent compound 4. The replacement of the C-5 A-acetyl moiety with a A-trifluoroacetyl group resulted in the most potent inhibitor of this series, 2-deoxy-2,3-didehydro-A-trifluoroacetylneuraminic acid 10 [A] 8 x 10 M (A/Nl)] (Meindl et al. 1974). While these C-5 modified compounds were also very effective in cell culture assays (Palese et al. 1974a Palese and Compans 1976), none, including the parent... 

The discovery of the potent in vitro sialidase inhibitory activity and in vivo efficacy of zanamivir 12, and the increasing availability of 3D structural data for influenza virus sialidases in the 1990s, particularly with Neu5Ac and various inhibitors bound into the active site, provided a platform for further drug discovery efforts targeting... 

Compound 34 (BCZ-1812, RWJ-270201, peramivir) showed selective inhibition of influenza virus sialidases over bacterial and mammalian sialidases (Babu et al. 2000 Bantia et al. 2001 Sidwell and Smee 2002). Successful inhibition of influenza virus infectivity in vitro (Smee et al. 2001) and upon oral administration in vivo [mice (Bantia et al. 2001) and ferrets, reviewed in Sidwell and Smee 2002] led to human clinical trials of orally administered peramivir (Barroso et al. 2005). While orally administrated peramivir successfully completed animal studies and Phase I and Phase II clinical trials, in which the compound was showing neither major side effects nor toxicity (Sidwell and Smee 2002), preliminary results of the Phase III trials (June 2002) demonstrated no statistically significant difference in the primary efficacy endpoint, possibly due to low bioavailability (Barroso et al. 2005). 

Ives JA, Carr JA, Mendel DB, Tai CY, Lambkin R, Kelly L, Oxford JS, Hayden FG, Roberts NA (2002) The H274Y mutation in the influenza A/HINI neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo. Antiviral Res 55 307-317... 

Mishin VP, Hayden FG, Gubareva LV (2005) SusceptibUities of antiviral-resistant influenza viruses to novel neuraminidase inhibitors. Antimicrob Agents Chemother 49 4515 520 Molla A, Kati W, Carrick R, Steffy K, Shi Y, Montgomery D, Gusick N, Stoll VS, Stewart KD, Ng TI, Maring C, Kempf DJ, Kohlbrenner W (2002) In vitro selection and characterization of influenza A. (A/N9) virus variants resistant to a novel neuraminidase inhibitor, A-315675. J Virol 76 5380-5386... 

Smee DE, Huffman JH, Morrison AC, Barnard DL, Sidwell RW (2001) Cyclopentane neuraminidase inhibitors with potent in vitro anti-influenza virus activities. Antimicrob Agents Chemother 45 743-748... 

Zhang J, Yu K, Zhu W, Jiang H (2006) Neuraminidase pharmacophore model derived from diverse classes of inhibitors. Bioorg Med Chem Lett 16 3009-3014 Ziircher T, Yates PJ, Daly J, Sahasrabudhe A, Walters M, Dash L, Tisdale M, McKimm-Breschkin JL (2006) Mutations conferring zanamivir resistance in human influenza virus N2 neuraminidases compromise virus fitness and are not stably maintained in vitro. J Antimicrob Chemother 58 723-732... 

Tai CY, Escarpe PA, Sidwell RW, WiUiams MA, Lew W, Wu H, Kim CU, Mendel DB (1998) Characterization of human influenza virus variants selected in vitro in the presence of the neuraminidase inhibitor GS 4071, Antimicrob Agents Chemother 42 3234-3241 Thomson MM, Najera R (2005) Molecular epidemiology of HlV-1 variants in the global AIDS pandemic an update. AIDS Rev 7 210-224... 

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