Treatment of epidemic and pandemic influenza with neuraminidase and M2 proton channel inhibitors

Oxford, John; Bossuyt, S.; Balasingam, Shobana; Mann, Alex; Novelli, P. C.S.; Lambkin, Robert

doi:10.1046/j.1469-0691.2003.00564.x

Cited by 103 publications

(93 citation statements)

References 37 publications

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“…For infl uenza treatment, there are two types of anti-infl uenza drug: amantadine and neuraminidase inhibitors (oseltamivir and zanamivir) (Monto 2003;Oxford et al 2003;Moscona 2005;Oxford 2005;Jefferson et al 2006). Amantadine is effective for treatment of infl uenza infl uenza A or B infections.…”

confidence: 99%

Effectiveness of Oseltamivir Treatment among Children with Influenza A or B Virus Infections during Four Successive Winters in Niigata City, Japan

Sato

Saito

Sato³

et al. 2008

Tohoku J. Exp. Med.

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Oseltamivir has been used for treatment of infl uenza A and B infections, but recent reports documented that it was less active against the latter. We compared the effectiveness of oseltamivir in children between laboratory confi rmed infl uenza A and B over 4 infl uenza seasons from 2001 to 2005 in a pediatric clinic in Japan. Among 1,848 patients screened, 299 infl uenza A and 209 infl uenza B patients were administered oseltamivir (treated groups), and 28 infl uenza A and 66 infl uenza B patients were assigned as non-treated groups. The duration of fever, defi ned as period when patients had the maximum temperature higher than 37.5°C in three-time measurements in a day after the clinic visit, was evaluated among the four groups. In uni-variate analysis, the duration of fever was shorter for treated group than non-treated for infl uenza A (1.8 ± 0.9 days vs 2.6 ± 1.3 days, p < 0.01), but it was not signifi cant for infl uenza B (2.4 ± 1.3 days vs 2.8 ± 1.2 days, p = 0.9). The fever duration was longer in treated infl uenza B than A patients ( p < 0.01). Multi-variate analysis indicated younger age ( < 6 years old) and higher body temperature at the clinic visit prolonged the duration of fever. Adjusted average duration of fever indicated that oseltamivir was effective for both types, but more effective on infl uenza A, and the benefi t increased for younger children. Our data provide evidence that oseltamivir is benefi cial for infl uenza infections, but the effectiveness is differed by type and age. infl uenza; anti-viral drugs; oseltamivir; children; effectiveness.Tohoku

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confidence: 99%

Effectiveness of Oseltamivir Treatment among Children with Influenza A or B Virus Infections during Four Successive Winters in Niigata City, Japan

Sato

Saito

Sato³

et al. 2008

Tohoku J. Exp. Med.

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“…Vaccinations remain the principle prophylactics for controlling influenza infections. Other prophylactic and therapeutic antiviral drugs are needed as well especially during an outbreak and for people with weaker immune systems, such as children, elderly, or individuals undergoing other medical treatments (2,3).…”

mentioning

confidence: 99%

High-throughput identification of compounds targeting influenza RNA-dependent RNA polymerase activity

Cheng

Lin

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

120

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As influenza viruses have developed resistance towards current drugs, new inhibitors that prevent viral replication through different inhibitory mechanisms are useful. In this study, we developed a screening procedure to search for new antiinfluenza inhibitors from 1,200,000 compounds and identified previously reported as well as new antiinfluenza compounds. Several antiinfluenza compounds were inhibitory to the influenza RNA-dependent RNA polymerase (RdRP), including nucleozin and its analogs. The most potent nucleozin analog, 3061 (FA-2), inhibited the replication of the influenza A/WSN/33 (H1N1) virus in MDCK cells at submicromolar concentrations and protected the lethal H1N1 infection of mice. Influenza variants resistant to 3061 (FA-2) were isolated and shown to have the mutation on nucleoprotein (NP) that is distinct from the recently reported resistant mutation of Y289H [Kao R, et al. (2010) Nat Biotechnol 28:600]. Recombinant influenza carrying the Y52H NP is also resistant to 3061 (FA-2), and NP aggregation induced by 3061 (FA-2) was identified as the most likely cause for inhibition. In addition, we identified another antiinfluenza RdRP inhibitor 367 which targets PB1 protein but not NP. A mutant resistant to 367 has H456P mutation at the PB1 protein and both the recombinant influenza and the RdRP expressing the PB1 H456P mutation have elevated resistance to 367. Our high-throughput screening (HTS) campaign thus resulted in the identification of antiinfluenza compounds targeting RdRP activity.high-throughput screening | antiinfluenza | influenza NP | influenza PB1 | chemical genetics

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“…Amantadine has been shown to be effective for treatment and prevention of human infl uenza A virus infections (Monto and Arden 1992;Oxford et al 2003). In Japan, the drug was approved for the treatment of infl uenza A in November 1998. lected from patients for screening with infl uenza rapid tests.…”

confidence: 99%

Recurrence and Persistence of Fever in Children Who Developed Amantadine-Resistant Influenza Viruses after Treatment

Shobugawa

Saito

Sato³

et al. 2008

Tohoku J. Exp. Med.

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In recent years, a dramatic increase of amantadine-resistant infl uenza A has occurred globally, but limited data have been available on the clinical course of patients developed amantadine-resistant viruses. We compared fever reduction between patients who developed resistance or remained sensitive in a pediatric clinic in Niigata, Japan, from 2000 to 2006. A total of 2,802 clinical samples were collected from patients who visited the pediatric outpatient clinic with infl uenza like illness during the seven infl uenza epidemic seasons. Patients were divided into 4 groups and analyzed for the fever reduction after amantadine treatment: emerged amantadine-resistant (n = 15); amantadine-sensitive (n = 35); patients administered no antiviral drugs (n = 42); and oseltamivir-treated patients (n = 320), which served as references. All 4 groups showed alleviation of fever up to day 3. The amantadine-resistant group had a signifi cant recurrence of fever on day 4 and/or 5, and as a consequence, the course of illness was prolonged. Considering the pattern of fever, recurrent and persistent patterns were found signifi cantly at higher rates in children with emerged resistant virus compared to other groups, and the age tended to be younger in amantadine-resistant compared to amantadine-sensitive group (3.9 ± 3.0 vs 6.7 ± 4.1 years old, n.s.). Therefore, we concluded that younger children were prone to develop amantadine-resistance after treatment and showed a signifi cant recurrence of fever on day 4 and/or 5, and the course of illness was consequently prolonged. infl uenza; amantadine; infl uenza; amantadine; antiviral-resistance; children; recurrence of fever.Tohoku

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Treatment of epidemic and pandemic influenza with neuraminidase and M2 proton channel inhibitors

Cited by 103 publications

References 37 publications

Effectiveness of Oseltamivir Treatment among Children with Influenza A or B Virus Infections during Four Successive Winters in Niigata City, Japan

Effectiveness of Oseltamivir Treatment among Children with Influenza A or B Virus Infections during Four Successive Winters in Niigata City, Japan

High-throughput identification of compounds targeting influenza RNA-dependent RNA polymerase activity

Recurrence and Persistence of Fever in Children Who Developed Amantadine-Resistant Influenza Viruses after Treatment

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