Antiviral Treatments for Influenza

AbstractInfluenza is an acute respiratory illness caused by the influenza A, B, and C viruses. It can occur in local outbreaks or seasonal epidemics, with possibility to spread worldwide in a pandemic when a novel strain with significant antigenic differences emerges. During the past years, several new drugs have become available, with different accessibility related to specific countries' approval. We have conducted a review of literature, analyzing the most recent data on efficacy and safety of drugs currently available to treat influenza, with a particular attention toward special populations. Efficacy and safety profile of neuraminidase inhibitors (oseltamivir, zanamivir, laninamivir, peramivir) and recently approved cap-dependent endonuclease inhibitor baloxavir marboxil are reported in literature, but still little information is available about special populations such as critically ill patients and patients with a history of chronic respiratory disease. Moreover, the emergence of strains with reduced or no susceptibility to current drugs is a matter of concern, suggesting the need of constant monitoring of viral variants.

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Relation of Airway Responsiveness to Methacholine to Parent and Child Reporting of Symptoms Suggecting Asthma

Canadian Respiratory Journal ◽

10.1155/1996/631713 ◽

1996 ◽

Vol 3 (2) ◽

pp. 115-123 ◽

Cited By ~ 3

Author(s):

JM FitzGerald ◽

DE Fester ◽

MM Morris ◽

M Schulzer ◽

FE Hargreave ◽

...

Keyword(s):

Sensitivity And Specificity ◽

Roc Curve ◽

Airway Hyperresponsiveness ◽

Respiratory Symptoms ◽

Respiratory Illness ◽

Airway Responsiveness ◽

Methacholine Challenge ◽

Cut Point ◽

The Past ◽

History Of

BACKGROUND:The lack of a relationship between airway responsiveness and respiratory symptoms in epidemiological studies of children may, in part, reflect inaccuracies in symptom reporting or inadequate knowledge by the parent of the child's symptoms.OBJECTIVE:To relate airway responsiveness to methacholine in children with symptoms of respiratory illness in the child as reported by the parent and as reported by the child.POPULATION:Eight- to 10-year-old (n=290) randomly sampled schoolchildren.SETTING:Seven randomly selected schools in Ontario.METHODS:Parents completed a mailed questionnaire regarding the child's respiratory health. Children completed a similar interview-administered questionnaire at school and underwent methacholine challenge testing by the tidal breathing method.RESULTS:The cumulative prevalence of a history of physician-diagnosed asthma was 9.0%, and of any wheezing it was 25.5%. A further 9% of children reported wheezing not documented by their parent. Of 229 children consenting to methacholine challenge, 78 (34.1%) showed airway responsiveness in the range generally associated with asthma in adults (provocation concentration of methacholine causing a 20% fall [PC20] in forced expired volume in 1 s [FEV1] 8 mg/mL or less); half of these children had no history of respiratory symptoms reported by the parent. The sensitivity of airway hyperresponsiveness defined by a cut-point for PC208 mg/mL or less in relation to any history of recurrent wheezing reported by the parent was 48% and did not improve if only symptoms within the past year were considered (sensitivity 44%); the specificity of the test for parent-reported symptoms ever was 71%, and 68% in those with symptoms in the past year. None of these sensitivities or specificities was increased by using symptoms reported by the child or by combining parent and child reported symptoms. Receiver operating characteristic (ROC) curves for sensitivity and specificity of the methacholine test were constructed for parent and child reports of symptoms. For all symptom strata, the cut-point of PC20producing optimal balance of sensitivity and specificity was between 4 and 8 mg/mL. A parental questionnaire positive for physician-diagnosed asthma was strongly related to methacholine response, producing an ROC curve with an area significantly different from 0.5 (P=0.006), as did all parent-reported wheezing (P=0.009). If the child reported asthma, there was an equally strong relationship, with a positive ROC curve (P=0.001), as there was for all child-reported wheezing (P=0.048).CONCLUSIONS:Airway hyperresponsiveness to methacholine in children relates closely with asthma and wheezing reported by either the parent or the child. In addition, the results confirm that respiratory symptoms and airway hyperresponsiveness are common in Canadian children, and that airway hyperresponsiveness may be found in children with no history of respiratory illness either at present or in the past.

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Phytoncides: history and application prospects

Bacteriology ◽

10.20953/2500-1027-2020-3-60-67 ◽

2020 ◽

Vol 5 (3) ◽

pp. 60-67

Author(s):

S.A. Chubatova ◽

◽

Keyword(s):

Key Words ◽

Medical Practice ◽

Antibacterial Agents ◽

New Drugs ◽

The Past ◽

History Of ◽

Ecology Program ◽

Application Prospects

A brief informational material on the history of the use of phytoncides in medical practice over the past few centuries and the results of our own research on the study of the properties of new drugs based on phytoncides in liposomes is proposed. The effectiveness of phytoncides use for 20 years within the framework of the «Indoor Airspace Ecology» program indicates that this direction is promising. Key words: phytoncides, liposomes, antibacterial agents

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Fate of Neuraminidases of Influenza A Viruses

E3S Web of Conferences ◽

10.1051/e3sconf/202021803053 ◽

2020 ◽

Vol 218 ◽

pp. 03053

Author(s):

Shaomin Yan ◽

Guang Wu

Keyword(s):

Influenza A ◽

Large Scale ◽

Small Scale ◽

Influenza A Viruses ◽

Simple Method ◽

The Past ◽

Current State ◽

Pair Probability ◽

History Of ◽

Near Future

The current COVID-19 pandemic creates the biggest health and economic challenges to the world. However, not much knowledge is available about this coronavirus, SARS-CoV-2, because of its novelty. Indeed, it necessarily knows the fate of proteins generated by SARS-CoV-2. Anyway, before a large-scale study on proteins from SARS-CoV-2, it would be better to conduct a small-scale study on a well-known protein from influenza A viruses, because both are positive-sense RNA viruses. Thus, we applied a simple method of amino-acid pair probability to analyze 94 neuraminidases of influenza A viruses for better understanding of their fate. The results demonstrate three features of these neuraminidases: (i) the N1 neuraminidases are more susceptible to mutations, which is the current state of the neuraminidases; (ii) the N1 neuraminidases have undergone more mutations in the past, which is the history of the neuraminidases; and (iii) the N1 neuraminidases have a larger potential towards future mutations, which is the future of the neuraminidases. Moreover, our study reveals two clues on the mutation tendency, i.e. the mutations represent a degeneration process, and chickens, ducks and geese are rendered more susceptive to mutation. We hope to apply this approach to study the proteins from SARS-CoV-2 in near future.

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Emerging zoonosis of a novel avian influenza A (H7N9) Virus. Are we prepared in the neotropics?

Revista Mvz Córdoba ◽

10.21897/rmvz.164 ◽

2013 ◽

pp. 3437-3438

Author(s):

Salim Mattar V ◽

Marco González T

Keyword(s):

Avian Influenza ◽

Influenza A ◽

Specific Treatment ◽

Respiratory Illness ◽

High Morbidity ◽

H7n9 Virus ◽

The Past ◽

The People ◽

Human Infections ◽

Severe Respiratory Illness

Zoonotic diseases represents a 78% of emerging and reemerging diseases, virus has an important proportion in zoonosis. We are not amazing anymore, we frequently see new virus that suddenly appears producing high morbidity and mortality, and all of them have non-specific treatment to try stopping them. The entire recent virus that came to our modern societies, were original from animals.The first human infections with a novel avian influenza A (H7N9) virus were described in China in March 2013 (1-3). The virus was detected in poultry (1-3). Many of the people infected (77%) with H7N9 have been reported to have contact with poultry. While mild illness in human cases has been seen, most patients have had severe respiratory illness and some people have died. No cases of H7N9 outside of China have been reported yet. The new H7N9 virus has not been detected in people or birds in the neotropics (1-3).Human infections with avian influenza occur most commonly after exposure to infected poultry (1-3). Limited person-to-person spread of bird flu is believed to have occurred rarely in the past, most notably with avian influenza A (H5N1). Based on this previous experience with avian influenza A (H5N1), some limited human-to-human spread of this H7N9 virus would not be surprising. Most important, however, is that this transmission not be sustained (1-3).

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Discovery of a Novel Tetrapeptide Against Influenza A Virus: Rational Design, Synthesis, Bioactivity Evaluation and Computational Studies

10.20944/preprints202106.0735.v1 ◽

2021 ◽

Author(s):

Maria Carmina Scala ◽

Mariangela Agamennone ◽

Agostina Pietrantoni ◽

Veronica Di Sarno ◽

Alessia Bertamino ◽

...

Keyword(s):

Influenza A ◽

Rational Design ◽

Respiratory Illness ◽

New Drugs ◽

Bovine Lactoferrin ◽

Computational Studies ◽

Cell Infection ◽

Design Synthesis ◽

Influenza Activity ◽

Reference Peptide

Influenza is a highly contagious, acute respiratory illness, which represents one of the main health issues worldwide. Even though some antivirals are available, the alarming increase of virus strains resistant to them highlights the need to find new drugs. Previously, Superti et al. have deeper investigated the mechanism of the anti-Influenza virus effect of bovine Lactoferrin (bLf) and the role of its tryptic fragments (the N and C-lobes) in the antiviral activity. Recently, through a truncation library, we identified the tetrapeptides, SKHS (1) and SLDC (2), derived from bLf C-lobe fragment 418-429, which were able to bind hemagglutinin (HA) and inhibit cell infection in a concentration range of femto- to picomolar. Starting from these results, in this work, we initiated a systematic SAR study on the peptides mentioned above, through an Alanine scanning approach. We carried out binding affinity measurements by microscale thermophoresis (MST) and Surface Plasmon Resonance (SPR), and hemagglutination inhibition (HI) and virus neutralization (NT) assays on synthesized peptides. Computational studies were performed to identify possible lig-and-HA interactions. Results obtained led to the identification of an interesting peptide endowed with broad anti-Influenza activity and able to inhibit viral infection to a greater extent of reference peptide.

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A network meta-analysis of the efficacy and safety of baloxavir marboxil versus neuraminidase inhibitors for the treatment of influenza in otherwise healthy patients

Terapevticheskii arkhiv ◽

10.26442/00403660.2020.11.000870 ◽

2020 ◽

Vol 92 (11) ◽

pp. 122-131

Author(s):

Vanessa Taieb ◽

Hidetoshi Ikeoka ◽

Fang-Fang Ma ◽

Katarzyna Borkowska ◽

Samuel Aballea ◽

...

Keyword(s):

Influenza A ◽

Meta Analysis ◽

Virus Titer ◽

Similar Efficacy ◽

The Other ◽

Efficacy And Safety ◽

Viral Shedding ◽

Randomized Controlled ◽

Dependent Endonuclease ◽

The Mean

Aim. Baloxavir marboxil (baloxavir) is the first cap-dependent endonuclease inhibitor being studied for the treatment of influenza in single oral dosing regimen. This network meta-analysis (NMA) evaluated the efficacy and safety of baloxavir compared to other antivirals for influenza in otherwise healthy patients. Methods. A systematic literature review was performed on 14 November 2016 in Medline, Embase, CENTRAL, and ICHUSHI to identify randomized controlled trials assessing antivirals for influenza. A NMA including 22 trials was performed to compare the efficacy and safety of baloxavir with other antivirals. Results. The time to alleviation of all symptoms was significantly shorter for baloxavir compared to zanamivir (difference in median time 19.96 h; 95% CrI [3.23, 39.07]). The time to cessation of viral shedding was significantly shorter for baloxavir than zanamivir and oseltamivir (47.00 h; 95% CrI [28.18, 73.86] and 56.03 h [33.74, 87.86], respectively). The mean decline in virus titer from baseline to 24 h was significantly greater for baloxavir than for the other drugs. Other differences in efficacy outcomes were not significant. No significant differences were found between baloxavir and the other antivirals for safety, except total drug-related adverse events where baloxavir demonstrated a decrease compared to oseltamivir and laninamivir. Conclusion. The NMA suggests that baloxavir demonstrated better or similar efficacy results compared to other antivirals with a comparable safety profile. Baloxavir led to a significant decrease in viral titer versus zanamivir, oseltamivir and peramivir and decreased viral shedding versus zanamivir and oseltamivir.

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Efficacy and safety of once-monthly ibandronate treatment in patients with low bone mineral density – ESTHER study: 24 months of follow-up

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1212722s ◽

2012 ◽

Vol 140 (11-12) ◽

pp. 722-727 ◽

Cited By ~ 2

Author(s):

Katarina Simic-Pasalic ◽

Study ESTHER

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Economic Problem ◽

Activity Level ◽

New Drugs ◽

Efficacy And Safety ◽

Mineral Density ◽

Low Bone Mineral Density ◽

History Of

Introduction. Osteoporosis is a major health and economic problem worldwide. The use of new drugs, such as ibandronate, is aimed at improving treatment of osteoporosis and currently poor compliance with BP therapy. Objective. To investigate efficacy and safety of ibandronate applied monthly, orally, in women with low bone mineral density (BMD). Methods. The prospective study was conducted in 34 centers in Serbia and included 77 women treated for 24 months with monthly ibandronate. The efficacy of treatment was assessed by change in bone mass values obtained by BMD measurement at the end of 24 months follow-up versus baseline and 12-months follow-up values. Compliance and safety, i.e. adverse effects (AE) were recorded. Results. Participants were postmenopausal (96%), osteoporotic (79.7%) females, diagnosed by lumbar spine DXA measurement (81%), with history of prior BP therapy in 33.8% women. The physical activity level significantly increased to the substantial level of activity (5.2% vs. 21.3%, p=0.003) during the study. After 12 and 24 months of treatment, BMD values significantly increased (p=0.002 and p<0.001). BP experienced patients improved more than BP na?ve patients at both time points (p=0.012 and p=0.027, respectively). During the second 12 months of treatment the adherence was 96%; AE were recorded as mild gastrointestinal disturbances in 3.9%. Conclusion. Treatment by using ibandronate once monthly for 24 months was generally well tolerated and led to a significant increase in BMD in women with low BMD.

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Therapeutic possibilities of topical corticosteroids in modern clinical practice

Medical Council ◽

10.21518/2079-701x-2020-12-36-45 ◽

2020 ◽

pp. 36-45

Author(s):

T. A. Belousova ◽

M. V. Kail

Keyword(s):

Clinical Practice ◽

Subcutaneous Tissue ◽

Import Substitution ◽

New Drugs ◽

Advanced Technology ◽

Efficacy And Safety ◽

Topical Corticosteroids ◽

Number Of Patients ◽

History Of ◽

History Of Use

Over the past decade, dermatological practice has seen an increase in the number of patients suffering from skin and subcutaneous tissue diseases. Annually, 6.4-6.9 million new cases of this group of diseases are registered, which encourages the constant search for new drugs and the continuous improvement of methods and schemes of application of proven drugs. Topical corticosteroids, despite more than 65 years of history of use in the treatment of patients with steroid-sensitive dermatoses, have not lost their relevance. At present, they have no therapeutic alternative in terms of speed of onset and anti-inflammatory activity, so they are essential in the treatment of many skin pathologies. One of the trends in modern pharmacology is not so much the production of new active molecules of TCS or their modifications, as the creation of new pharmacological forms of known molecules - micronized, nanonized, which give the drug the most important property -increased bioavailability. This advanced technology is actively used in the production of domestic topical drugs of Akriderm lines, which make a major contribution to the program of import substitution and drug availability for the population. The optimal combination of ingredients of the foundation of these drugs complements and potentiates the therapeutic effect of steroid. For more than 30 years in clinical practice, a combination of 0.05% betamethasone dipropionate, 0.1% gentamicin sulfate and 1% clotrimazole (Triderm, Akriderm GK) is used. Many years of positive clinical experience of dermatologists using this fixed combination proves the validity of its use in many clinical situations when bacterial and fungal infection is involved. An open randomized comparative study conducted by Russian dermatologists on the efficacy and safety of Akriderm GK (cream) and Triderm (cream) in the complex treatment of eczema showed similar profiles of high clinical efficacy and safety of both drugs.

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Discovery of a Novel Tetrapeptide against Influenza A Virus: Rational Design, Synthesis, Bioactivity Evaluation and Computational Studies

Pharmaceuticals ◽

10.3390/ph14100959 ◽

2021 ◽

Vol 14 (10) ◽

pp. 959

Author(s):

Maria Carmina Scala ◽

Mariangela Agamennone ◽

Agostina Pietrantoni ◽

Veronica Di Sarno ◽

Alessia Bertamino ◽

...

Keyword(s):

Influenza A ◽

Rational Design ◽

Respiratory Illness ◽

New Drugs ◽

Bovine Lactoferrin ◽

Computational Studies ◽

Cell Infection ◽

Design Synthesis ◽

Influenza Activity ◽

Reference Peptide

Influenza is a highly contagious, acute respiratory illness, which represents one of the main health issues worldwide. Even though some antivirals are available, the alarming increase in virus strains resistant to them highlights the need to find new drugs. Previously, Superti et al. deeply investigated the mechanism of the anti-influenza virus effect of bovine lactoferrin (bLf) and the role of its tryptic fragments (the N- and C-lobes) in antiviral activity. Recently, through a truncation library, we identified the tetrapeptides, Ac-SKHS-NH2 (1) and Ac-SLDC-NH2 (2), derived from bLf C-lobe fragment 418–429, which were able to bind hemagglutinin (HA) and inhibit cell infection in a concentration range of femto- to picomolar. Starting from these results, in this work, we initiated a systematic SAR study on the peptides mentioned above, through an alanine scanning approach. We carried out binding affinity measurements by microscale thermophoresis (MST) and surface plasmon resonance (SPR), as well as hemagglutination inhibition (HI) and virus neutralization (NT) assays on synthesized peptides. Computational studies were performed to identify possible ligand–HA interactions. Results obtained led to the identification of an interesting peptide endowed with broad anti-influenza activity and able to inhibit viral infection to a greater extent of reference peptide.

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On The Possibility of an Autonomous History of Modern Southeast Asia

Journal of Southeast Asian History ◽

10.1017/s0084255900007944 ◽

1961 ◽

Vol 2 (2) ◽

pp. 73-105 ◽

Cited By ~ 2

Author(s):

John R. W. Small

Keyword(s):

Southeast Asia ◽

Contemporary History ◽

The Past ◽

History Of

It is generally accepted that history is an element of culture and the historian a member of society, thus, in Croce's aphorism, that the only true history is contemporary history. It follows from this that when there occur great changes in the contemporary scene, there must also be great changes in historiography, that the vision not merely of the present but also of the past must change.

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