Influenza-A virus

AMANTADINE The nurse administers this drug for the prevention or treatment of respiratory tract illness caused by influenza A virus. Some patients are prescribed this drug to manage extrapyramidal effects caused by drugp used to treat Parkinsonism (See Chaps. 29 and 32). The nurse should protect the capsules from moisture to prevent deterioration. When the drug is administered for symptoms of influenza, it is important to start therapy within 24 to 48 hours after symptoms begin. 

Bright RA, Shay DK, Shu B, Cox NJ, Klimov AI (2006) Adamantane resistance among influenza A viruses isolated early during the 2005-2006 influenza season in the United States. JAMA 295 891-894... 

Fig. 3 Sialidase inhibitor Neu5Ac2en 4 bound in the active site of influenza A virus sialidase (from PDB structure IfSb (Smith et al, 2001)), Left Stick model of 4 surrounded by some important active site residues. Right Electrostatic potential surface rendering of the active site (blue -positive, red - negative), (Amino acid numbering for influenza A/N2 sialidase is used throughout this review)...

Fig. 5 Key interactions of 4-deoxy-4-guanidino-Neu5Ac2en (zanamivir) 12 with the active site of influenza A virus sialidase [Figure generated from crystal strucmre data (PDB - Innc) using LIGPLOT (Wallace et al. 1995)]. To the right is shown zanamivir 12 in the same orientation...

Fig. 6 Superimposition of inhibitors and key active site residues from crystal structures of oseltamivir carboxylate 18 brown carbons, PDB - 2qwk) and Neu5Ac2en 4 (green carbons, PDB - IfSb) in complex with influenza A virus siaMdase. Note the alternative conformations of the...

Fig. 9 Diagrammatic representation of influenza A virus active site indicating the amino acid residues that have shown mutation under drug pressure. Oseltamivir carboxylate 18 is shown in the active site...

Calfee DP, Peng AW, Cass LM, Lobo M, Hayden FG (1999) Safety and efficacy of intravenous zanamivir in preventing experimental human influenza A virus infection. Antimicrob Agents Chemother 43 1616-1620... 

Hagiwara T, Kijima-Suda I, Ido T, Ohrui H, Tomita K (1994) Inhibition of bacterial and viral sialidases by 3-fluoro-V-acetyIneuraminic acid, Carbohydr Res 263 167-172 Haskell TH, Peterson FE, Watson D, Plessas NR, Culbertson T (1970) Neuraminidase inhibition and viral chemotherapy, J Med Chem 13 697-704 Hatakeyama S, Sugaya N, Ito M, Yamazaki M, Ichikawa M, Kimura K, Kiso M, Shimizu H, Kawakami C, Koike K, Mitamura K, Kawaoka Y (2007) Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors, JAMA 297 1435-1442 Hay AJ (1992) The action of adamantanamines against influenza A viruses inhibition of the M2 ion channel protein, Semin Virol 3 21-30... 

Kiso M, Mitamura K, Sakai-Tagawa Y, Shiraishi K, Kawakami C, Kimura K, Hayden FG, Sugaya N, Kawaoka Y (2004) Resistant influenza A viruses in children treated with oseltamivir descriptive study. Lancet 364 759-765... 

Smee DE, Bailey KW, Morrison AC, SidweU RW (2002) Combination treatment of influenza A virus infections in ceU culture and in mice with the cyclopentane neuraminidase inhibitor RWJ-270201 and ribavirin. Chemotherapy 48 88-93... 

Suzuki Y, Ito T, Suzuki T, HoUand RE Jr, Chambers TM, Kiso M, Ishida H, Kawaoka Y (2000) Sialic acid species as a determinant of the host range of influenza A viruses. J Virol 74 11825-11831... 

Wang S-Q, Du Q-S, Chou K-C (2007) Study of drug resistance of chicken influenza A virus (H5N1) from homology-modeled 3D structures of neuraminidases. Biochem Biophys Res Commun 354 634-640... 

Avian influenza A virus No significant protection Isomura et al. 1982 Phillpotts et al. 1984... 

Hayden FG, Belshe RB, Clover RD, Hay AJ, Oakes MG, Soo W (1989) Emergence and apparent transmission of rimantadine-resistant influenza A virus in families. N Engl J Med 321 1696-1702... 

Extensive investigations have been performed related to the synthesis of new adamantane derivatives with better therapeutic actions and less adverse effects. For example, it has been proved that adamantylamino-pyrimidines and -pyridines are strong stimulants of mmor necrosis factor-a (TNF-a) [132]. TNF is a substance that can improve the body s namral response to cancer by killing cancer cells. Another example is 1,6-diaminodiamantane [87], which possesses an antitumor and antibacterial activity. Also, many derivatives of aminoadamantanes have antiviral activity like 3-(2-adamantyl) pyrolidines with two pharmacophoric amine groups, which have antiviral activity against influenza-A virus [133]. 

Buffinton, G.D., Christen, S., Peterhans, E. and Stocker, R. (1992). Oxidative stress in lungs of mice infected with influenza A virus. Free Rad. Res. Commun. 16, 99-110. 

Viruses are a common cause of CAP in children (-65%) and much less common in adults ( 15%).8 Viruses often associated with pneumonia in adults include influenza A and B and adenoviruses, whereas less common causes include rhinoviruses, enteroviruses, cytomegalovirus, varicella-zoster virus, herpes simplex virus, and others. In children, viral pneumonia is caused more commonly by respiratory syncyntial virus, influenza A virus, and parainfluenza virus. The viruses associated with CAP in adults are much less common causes of pneumonia in children. 

Debes GF, Bonhagen K, Wolff T, et al. CC chemokine receptor 7 expression by effector/memory CD4+ T cells depends on antigen specificity and tissue localization during influenza A virus infection. J Virol 2004 78 7528-7535. 

Domino reactions are also used in the development of new and potent pharmaceuticals, which is an important target in organic synthesis. The following example by Katoh and coworkers presents an impressive approach to the tetracyclic core structure of the novel anti-influenza A virus agent, stachyflin (1-152), using as key feature a new Lewis acid-induced domino epoxide-opening/rearrangement/cy-... 

Hirsutine (2-795), which belongs to the corynanthe subgroup of the indole alkaloids, was isolated from the plant Uncaria rhynchophylla MIQ and used for the preparation of the old Chinese folk medicine Kampo [397]. It is of pharmacological interest as it shows a strong inhibitory effect on the influenza A virus (subtype H3N2) with an EC50 = 0.40-0.57 pg ml. which is about 11- to 20-fold higher than that of the clinically used ribavirin [398]. 

Myc A, Anderson MJ, Baker JRJ. Optimization of in situ cellular ELISA performed on influenza A virus-infected monolayers for screening of antiviral agents. /. Virol. Methods 1999 77 165-177. 

R. Roy, D. Zanini, S. J. Meunier, and A. Romanowska, Solid phase synthesis of dendritic sialoside inhibitors of influenza A virus haemagglutinin, J. Chem. Soc. Chem. Commun. (1993) 1869-1872. 

The adamantanes, amantadine and rimantadine, are currently not recommended for prophylaxis or treatment in the United States because 92% of the circulating influenza A viruses are resistant to these agents. 

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