Influenza virus antiviral agents

It may be possible to increase the utility of our resources to treat influenza virus infection through combinations of antiviral agents with different modes of action (discussed in Cinatl et al. 2007a De Clercq and Neyts 2007). The sialidase inhibitors, for example, may be able to be used in conjunction with the adamantane-based M2 ion channel inhibitors (Govorkova et al. 2004 Ilyushina et al. 2006), with Ribavirin (Smee et al. 2002) or with non-influenza virus specific therapeutics such as anti-inflammatory drugs (Carter 2007). Combination therapy may also reduce the potential of resistance development (Ilyushina et al. 2006). 

Hurt AC, lanneUo P, Jachno K, Komadina N, Hampson AW, Barr IG, McKimm-Breschkin JL (2006) Neuraminidase inhibitor-resistant and -sensitive influenza B viruses isolated from an untreated human patient, Antimicrob Agents Chemother 50 1872-1874 Hurt AC, Selleck P, Komadina N, Shaw R, Brown L, Barr IG (2007) Susceptibility of highly pathogenic A(H5N1) avian influenza viruses to the neuraminidase inhibitors and adamantanes. Antiviral Res 73 228-231... 

Kim CU, Lew W, Wilhams MA, Wu H, Zhang L, Chen X, Escarpe PA, Mendel DB, Laver WG, Stevens RC (1998) Structure-activity relationship studies of novel carbocyclic influenza neuraminidase inhibitors, J Med Chem 41 2451-2460 Kim CU, Chen X, Mendel DB (1999) Neuraminidase inhibitors as anti-influenza virus agents. Antiviral Chem Chemother 10 141-154... 

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... 

Yen H-L, Herlocher LM, Hoffmann E, Matrosovich MN, Monto AS, Webster RG, Govorkova EA (2005) Neuraminidase inhibitor-resistant influenza viruses may differ substantially in fitness and transmissibility. Antimicrob Agents Chemother 49 4075 084 Zambon M, Hayden EG (2001) Position statement global neuraminidase inhibitor susceptibility network. Antiviral Res 49 147-156... 

Kim CU, Chen X, Mendel DB. Neuraminidase inhibitors as anti-influenza virus agents. Antiviral Chem Chemother 1999 10 141-154. 

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. 

This chapter describes the basic characteristics of viruses and the relatively limited number of drugs that can act selectively as antiviral agents. Methods of preventing viral infections (antiviral vaccines) are also briefly discussed. Finally, the current methods of treating a specific viral-induced disease—AIDS—are presented. Rehabilitation specialists often treat patients who are in the active stages of a viral infection, as well as those suffering from the sequelae of viral disorders, such as gastroenteritis, encephalitis, and influenza. Hence, the pharmacotherapeutic treatment and prophylaxis of viral infections should concern physical therapists and occupational therapists. 

Viral respiratory tract infections for which treatments exist include those of influenza types A and B, and respiratory syncytial virus (RSV). [Note Immunization against influenza A is the preferred approach. However, antiviral agents are employed when patients are allergic to the vaccine or when the outbreak is due to an immunologic variant of the virus not covered by vaccines, or when outbreaks occur among unvaccinated individuals at risk who are in closed settings, for example, in a nursing home.]... 

In many viral infections the clinical symptoms appear late in the course of the disease at a time when most of the virus particles have replicated. [Note This contrasts with bacterial diseases in which the clinical symptoms are usually coincident with bacterial proliferation.] At this late, symptomatic stage of the viral infection, administration of drugs that block viral replication have limited effectiveness. However, some antiviral agents are useful as prophylactic agents. For example, amantadine [a MAN ta deen] and its congener, rimantadine [rih MAN ta deen] have been shown to be equally effective in preventing influenza A infections. [Note Amantadine is also effective in the treatment of some cases of Parkinson s disease (see p. 87).]... 

Influenza is essentially an uncontrolled disease. Although vaccines are available and are used, their efficacy is limited. The antigenic variability of the virus has hampered production of a viable vaccine and precluded an eftective control. Ciurent vaccines are unlikely to be effective against a new pandemic strain whereas a good antiviral agent would have an enormous potential in such situations. 

The sialic acid analogs or glycomimetics, zanamivir (8)and oseltamivir (9), are members of a new class of antiviral agents that selectively inhibit the neuraminidase of both influenza A and B viruses. 

Oseltamivir phosphate is an antiviral agent that acts to inhibit influenza virus neuraminidase with possible alter-... 

Zanamivir is an antiviral agent that inhibits influenza virus neuraminidase, with the possibility of alteration of virus particle aggregation and release. It is indicated in uncomplicated acute illness caused by influenza A and B virus in adults and pediatric patients of at least 7 years of age who have been symptomatic for no longer than 2 days. 

Sulphated PS, potent antiviral agents, were also evaluated in vitro as inhibitors of influenza virus replication [119], The fact that the sulphated PS are inhibitory to some myxoviruses and retroviruses but not to others seems to depend on the composition of the amino acid sequences of the viral envelope glycoproteins that are involved in virus-cell binding and fusion [120],... 

Evidence of antiviral effects has especially been shown for St. John s Wort [2,3,10], Plant preparations with different chemical composition have been assayed against various viruses and both, hypericin and pseudohypericin, were found to be particularly effective as virucidal agents. The two compounds have been shown to be active against a broad range of viruses and retroviruses, such as herpes simplex virus types I and II, vesicular stomatitis and influenza viruses, cytomegalovyrus and human immunodeficiency virus-1 [2,3,10,91,92]. 

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