Antiviral Drugs in Influenza

Świerczyńska, Magdalena; Mirowska‐Guzel, Dagmara; Pindelska, Edyta

doi:10.3390/ijerph19053018

Cited by 53 publications

(46 citation statements)

References 116 publications

(302 reference statements)

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“…However, most of NA inhibitors developed so far are derivatives of commercial drugs. More detailed information about influenza virus NA inhibitors can be found in recent comprehensive reviews. ,, …”

Section: Discussionmentioning

confidence: 99%

“…Based on the already known inhibitors of human sialidases, a structure–activity relationship at C-4, C-5, C-7, and C-9 position is discussed in detail for the development of potent and selective inhibitors . More detailed information about these selective human sialidase inhibitors can be found in recent comprehensive reviews. ,, These sialidase inhibitors represent useful tools for elucidating the roles of human sialidases in health and disease. Their in vivo activities and therapeutic applications deserve further investigation.…”

Section: Discussionmentioning

confidence: 99%

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Sialidase Inhibitors with Different Mechanisms

et al. 2022

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Sialidases, or neuraminidases, are enzymes that catalyze the hydrolysis of sialic acid (Sia)-containing molecules, mostly removal of the terminal Sia (desialylation). By desialylation, sialidase can modulate the functionality of the target compound and is thus often involved in biological pathways. Inhibition of sialidases with inhibitors is an important approach for understanding sialidase function and the underlying mechanisms and could serve as a therapeutic approach as well. Transition-state analogues, such as anti-influenza drugs oseltamivir and zanamivir, are major sialidase inhibitors. In addition, difluoro-sialic acids were developed as mechanism-based sialidase inhibitors. Further, fluorinated quinone methide-based suicide substrates were reported. Sialidase product analogue inhibitors were also explored. Finally, natural products have shown competitive inhibiton against viral, bacterial, and human sialidases. This Perspective describes sialidase inhibitors with different mechanisms and their activities and future potential, which include transition-state analogue inhibitors, mechanism-based inhibitors, suicide substrate inhibitors, product analogue inhibitors, and natural product inhibitors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sialidase Inhibitors with Different Mechanisms

et al. 2022

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“…It has a low oral bioavailability (2–10%), therefore it works best when administered by oral inhalation. This allows to deposit approximately 78% of the drug in the mouth and throat, which is the primary site of influenza virus replication [ 57 ]. According to European Medicines Agency zanamivir is indicated for the treatment of influenza A and influenza B in adults and children with influenza-like symptoms while the influenza virus is present in their community.…”

Section: Treatment Options and Emerging Limitations In The Treatment ...mentioning

confidence: 99%

“…Oseltamivir’s bioavailability is significantly higher than zanamivir’s, reaching 80% [ 15 , 57 ]. The neuraminidase mutation related to the oseltamivir resistance was first detected in the A/H1N1 (A/Brisbane/59/2007-like) strain, which caused seasonal influenza in 2007.…”

Section: Treatment Options and Emerging Limitations In The Treatment ...mentioning

confidence: 99%

“…The concentration of the drug in the respiratory tract exceeds the IC 50 for influenza virus even up to 240 hours after inhalation. Its concentration in the respiratory tract was estimated to be 10,000 times higher than its concentration in plasma [ 57 ]. Laninamivir is an effective treatment for highly pathogenic avian influenza A/H5N1 and A/H1N1pdm09 viruses, as well as strains resistant to oseltamivir and zanamivir.…”

Section: Treatment Options and Emerging Limitations In The Treatment ...mentioning

confidence: 99%

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Evolution of Influenza Viruses—Drug Resistance, Treatment Options, and Prospects

Smyk

Szydłowska

Szulc

et al. 2022

IJMS

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Viral evolution refers to the genetic changes that a virus accumulates during its lifetime which can arise from adaptations in response to environmental changes or the immune response of the host. Influenza A virus is one of the most rapidly evolving microorganisms. Its genetic instability may lead to large changes in its biological properties, including changes in virulence, adaptation to new hosts, and even the emergence of infectious diseases with a previously unknown clinical course. Genetic variability makes it difficult to implement effective prophylactic programs, such as vaccinations, and may be responsible for resistance to antiviral drugs. The aim of the review was to describe the consequences of the variability of influenza viruses, mutations, and recombination, which allow viruses to overcome species barriers, causing epidemics and pandemics. Another consequence of influenza virus evolution is the risk of the resistance to antiviral drugs. Thus far, one class of drugs, M2 protein inhibitors, has been excluded from use because of mutations in strains isolated in many regions of the world from humans and animals. Therefore, the effectiveness of anti-influenza drugs should be continuously monitored in reference centers representing particular regions of the world as a part of epidemiological surveillance.

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An Observational Study on the Pharmacokinetics of Oseltamivir in Lactating Influenza Patients

Fodor,

Nagy,

Nógrádi

et al. 2023

Clin Pharma and Therapeutics

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Influenza infection may lead to serious complications in the postpartum period, therefore, oseltamivir treatment in these patients and their breastfed infants is of great importance. However, the pharmacokinetics of oseltamivir in postpartum lactating women with acute influenza infection, and the consequent infant exposure to oseltamivir are still unknown, and these data would help in assessing risk and the need for dose adjustment in breastfed infants.Six lactating women with influenza‐like symptoms, at a standard dose of 75 mg oral oseltamivir twice daily for 5 days, were recruited in this phase 4 clinical study during the 2011/2012 H1N1 pandemic seasons. Breast milk/colostrum and venous blood samples were taken at multiple time points, maternal urine samples were obtained from total output within the 12‐hour observational period following the 7th dose of oseltamivir.Oseltamivir phosphate (OP) reached a maximum 69.5±29.4 ng/mL concentration in breast milk, higher than that found in the plasma, and showed elimination within approximately 8 hours. Oseltamivir carboxylate (active metabolite of OP) showed a lower, nearly steady state concentration in breast milk during the observational period (Cmax=38.4±12.9 ng/mL). Based on estimated daily milk consumption of exclusively breastfed infants, their calculated daily exposure is less than 0.1% of the infant dose of oseltamivir for treatment of influenza as per marketing authorization.Here, we provide the first maternal breast milk pharmacokinetic data for oral multiple‐dose oseltamivir in lactating influenza patients and showed that its concentration in the breast milk is not sufficient to reach a therapeutic dose for breastfed infants.

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Antiviral Drugs in Influenza

Cited by 53 publications

References 116 publications

Sialidase Inhibitors with Different Mechanisms

Sialidase Inhibitors with Different Mechanisms

Evolution of Influenza Viruses—Drug Resistance, Treatment Options, and Prospects

An Observational Study on the Pharmacokinetics of Oseltamivir in Lactating Influenza Patients

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