Effect of the virostatic norakin® (triperiden) on influenza virus activities

Ott, Susanne; Wunderli‐Allenspach, Heidi

doi:10.1016/0166-3542(94)90050-7

Cited by 16 publications

(12 citation statements)

References 15 publications

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“…The vacuolar proton-ATPase (v-ATPase) responsible for this process might be considered as a target for chemotherapeutic intervention to prevent virus entry. Ott and WunderliAllenspach found that norakin (triperiden) inhibits influenza virus replication in cell culture by elevating the internal pH in the prelysosomal compartment [233]. It is noteworthy that two macrolide antibiotics, concanamycin A (47) and bafilomycin A1 (48), were identified as selective v-ATPase inhibitors.…”

Section: V-atpasementioning

confidence: 98%

Potential Targets and Their Relevant Inhibitors in Anti-influenza Fields

Gong¹,

Fang

Li³

et al. 2009

CMC

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Influenza is a disease for deeply affecting millions of people every year. Recently, there has been considerable concern regarding the highly pathogenic H5N1 avian influenza virus, and its human pandemic potential. With developments in viral biology, there are more novel antiviral strategies targeting these viruses. In this review, we will discuss several proven and potential anti-influenza targets, including viral factors (such as hemagglutinin (HA), M2 ion channel protein, RNA-dependent RNA polymerase (RdRp), nucleoprotein (NP), non-structural protein (NS) and neuraminidase (NA)) and host factors (such as v-ATPase, protease, inosine monophosphate dehydrogenase (IMPDH) and intracellular signalling cascades), and their relevant inhibitors.

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Section: V-atpasementioning

confidence: 98%

Potential Targets and Their Relevant Inhibitors in Anti-influenza Fields

Gong¹,

Fang

Li³

et al. 2009

CMC

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“…These are typically basic amine derivatives, which are only effective at concentrations too high to be considered of physiological relevance. For example, millimolar concentrations of the anti-parkinson agent norakin 21 35 and chloroquine 22 36 are thought to function in this fashion.…”

Section: P R O T E O L Y T I C C L E a V A G E O F H Amentioning

confidence: 99%

Anti‐influenza virus agents: Synthesis and mode of action

Lagoja

Clercq

2006

Medicinal Research Reviews

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Annual epidemics of influenza virus infection are responsible for considerable morbidity and mortality, and pandemics are much more devastating. Considerable knowledge of viral infectivity and replication has been acquired, but many details still have to be elucidated and the virus remains a challenging target for drug design and development. This review provides an overview of the antiviral drugs targeting the influenza viral replicative cycle. Included are a brief description of their chemical syntheses and biological activities. For other reviews, see References1-9.

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“…In subsequent studies it was determined that influenza viruses selected for resistance to norakin contained sequence changes in HA, some of which were identical to those found in the HA of viruses selected for resistance to high concentrations of amantadine (Prosch et al, 1988(Prosch et al, , 1990. Recently, norakin has been shown to elevate lysosomal pH, thus explaining its effects on virus entry (Ott & Wunderli-Allenspach, 1994 (Guinea & Carrasco, 1995) and to inhibit influenza A and B virus replication (Ochiai et al, 1995).…”

Section: Lysosomotropic Agentsmentioning

confidence: 99%

Approaches and Strategies for the Treatment of Influenza Virus Infections

Colacino

Staschke

Laver

1999

Antivir Chem Chemother

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Influenza A and B viruses belong to theOrthomyxoviridae family of viruses. These viruses are responsible for severe morbidity and significant excess mortality each year. Infection with influenza viruses usually leads to respiratory involvement and can result in pneumonia and secondary bacterial infections. Vaccine approaches to the prophy-laxis of influenza virus infections have been problematic owing to the ability of these viruses to undergo antigenic shift by exchanging genomic segments or by undergoing antigenic drift, consisting of point mutations in the haemagglutinin (HA) and neuraminidase (NA) genes as a result of an error-prone viral polymerase. Historically, antiviral approaches for the therapy of both influenza A and B viruses have been largely unsuccessful until the elucidation of the X-ray crystallographic structure of the viral NA, which has permitted structure-based drug design of inhibitors of this enzyme. In addition, recent advances in the elucidation of the structure and complex function of influenza HA have resulted in the discovery of a number of diverse compounds that target this viral protein. This review article will focus largely on newer antiviral agents including those that inhibit the influenza virus NA and HA. Other novel approaches that have entered clinical trials or been considered for their clinical utility will be mentioned. Keywords: Influenza virus; haemagglutinin; neuraminidase; amantadine; ribavirin; zanamivir; GS 4104Infection with influenza viruses can result in an infectious disease for which there is no adequate control. Killed influenza vaccines against this virus have been available for nearly 70 years but, on a community-wide basis, the use of these vaccines has not resulted in a significant decrease in the morbidity or mortality of this disease and has not alleviated the severe financial loss which occurs as a result of hospitalizations and lost productivity. Currently, the only compounds approved by the US FDA for the treatment of influenza infections are amantadine and rimantadine, both of which target the M2 ion channel protein of the virus (Pinto et al., 1992). However, these compounds are not effective against influenza B virus, which does not have an M2 ion channel. Also, virus mutants resistant to amantadine or rimantadine can be isolated readily from individuals treated with these drugs Hayden et al., 1989). Recently, it has been suggested that resistance to amantadine can be overcome by mixing amantadine with other amantadine derivatives that interfere with the ion channel function of M2 from amantadine-resistant viruses (Scholtissek et al., 1998). Ribavirin, a broad-spectrum antiviral agent Witkowski et al., 1972;Huffman et al., 1973;Oxford, 1975) has been considered for use against influenza A and B viruses, but the clinical trials of this compound have not been encouraging (Cohen et al., 1976;Togo & McCracken, 1976;Magnussen et al., 1977;Smith et al., 1980;Stein et al., 1987) and it has not been approved for the treatment of influenza virus infection.Hist...

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Effect of the virostatic norakin® (triperiden) on influenza virus activities

Cited by 16 publications

References 15 publications

Potential Targets and Their Relevant Inhibitors in Anti-influenza Fields

Potential Targets and Their Relevant Inhibitors in Anti-influenza Fields

Anti‐influenza virus agents: Synthesis and mode of action

Approaches and Strategies for the Treatment of Influenza Virus Infections

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