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Science Advances Feb 2024Seasonal or pandemic illness caused by influenza A viruses (IAVs) is a major public health concern due to the high morbidity and notable mortality. Although there are...
Seasonal or pandemic illness caused by influenza A viruses (IAVs) is a major public health concern due to the high morbidity and notable mortality. Although there are several approved drugs targeting different mechanisms, the emergence of drug resistance calls for new drug candidates that can be used alone or in combinations. Small-molecule IAV entry inhibitor, ING-1466, binds to hemagglutinin (HA) and blocks HA-mediated viral infection. Here, we show that this inhibitor demonstrates preventive and therapeutic effects in a mouse model of IAV with substantial improvement in the survival rate. When administered orally it elicits a therapeutic effect in mice, even after the well-established infection. Moreover, the combination of ING-1466 with oseltamivir phosphate or baloxavir marboxil enhances the therapeutic effect in a synergistic manner. Overall, ING-1466 has excellent oral bioavailability and in vitro absorption, distribution, metabolism, excretion, and toxicity profile, suggesting that it can be developed for monotherapy or combination therapy for the treatment of IAV infections.
Topics: Animals; Mice; Oseltamivir; Influenza A virus; Antiviral Agents; Oxazines; Pyridines; Thiepins; Dibenzothiepins; Morpholines; Pyridones; Triazines
PubMed: 38394202
DOI: 10.1126/sciadv.adk9004 -
Clinical Infectious Diseases : An... Aug 2023Understanding the changing epidemiology of adults hospitalized with coronavirus disease 2019 (COVID-19) informs research priorities and public health policies.
Changing Severity and Epidemiology of Adults Hospitalized With Coronavirus Disease 2019 (COVID-19) in the United States After Introduction of COVID-19 Vaccines, March 2021-August 2022.
INTRODUCTION
Understanding the changing epidemiology of adults hospitalized with coronavirus disease 2019 (COVID-19) informs research priorities and public health policies.
METHODS
Among adults (≥18 years) hospitalized with laboratory-confirmed, acute COVID-19 between 11 March 2021, and 31 August 2022 at 21 hospitals in 18 states, those hospitalized during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-predominant period (BA.1, BA.2, BA.4/BA.5) were compared to those from earlier Alpha- and Delta-predominant periods. Demographic characteristics, biomarkers within 24 hours of admission, and outcomes, including oxygen support and death, were assessed.
RESULTS
Among 9825 patients, median (interquartile range [IQR]) age was 60 years (47-72), 47% were women, and 21% non-Hispanic Black. From the Alpha-predominant period (Mar-Jul 2021; N = 1312) to the Omicron BA.4/BA.5 sublineage-predominant period (Jun-Aug 2022; N = 1307): the percentage of patients who had ≥4 categories of underlying medical conditions increased from 11% to 21%; those vaccinated with at least a primary COVID-19 vaccine series increased from 7% to 67%; those ≥75 years old increased from 11% to 33%; those who did not receive any supplemental oxygen increased from 18% to 42%. Median (IQR) highest C-reactive protein and D-dimer concentration decreased from 42.0 mg/L (9.9-122.0) to 11.5 mg/L (2.7-42.8) and 3.1 mcg/mL (0.8-640.0) to 1.0 mcg/mL (0.5-2.2), respectively. In-hospital death peaked at 12% in the Delta-predominant period and declined to 4% during the BA.4/BA.5-predominant period.
CONCLUSIONS
Compared to adults hospitalized during early COVID-19 variant periods, those hospitalized during Omicron-variant COVID-19 were older, had multiple co-morbidities, were more likely to be vaccinated, and less likely to experience severe respiratory disease, systemic inflammation, coagulopathy, and death.
Topics: Humans; Adult; Female; United States; Middle Aged; Aged; Male; COVID-19 Vaccines; COVID-19; SARS-CoV-2; Hospital Mortality; Oxygen
PubMed: 37255285
DOI: 10.1093/cid/ciad276 -
PloS One 2023Both physicians and patients are proactive towards managing seasonal influenza in Japan and six drugs are approved. Although many countries have national influenza...
BACKGROUND
Both physicians and patients are proactive towards managing seasonal influenza in Japan and six drugs are approved. Although many countries have national influenza surveillance systems, data on nationwide prescription practices of anti-influenza drugs are lacking. Therefore, we aimed to clarify the status of anti-influenza drug use in Japan by analyzing real-world data.
METHODS
This retrospective study analyzed open data from the National Database of Health Insurance Claims and Specific Health Checkups, which covers most claims data from national health insurance. We estimated the annual number of patients prescribed anti-influenza drugs, which drugs they were prescribed, the patients' age and sex distribution, drug costs, and regional disparities for the period 2014-2020.
RESULTS
For 2014-2019, an estimated 6.7-13.4 million patients per year were prescribed anti-influenza drugs, with an annual cost of 22.3-48.0 billion JPY (Japanese Yen). In addition, 21.1-32.0 million rapid antigen tests were performed at a cost of 30.1-47.1 billion JPY. In 2017, laninamivir was the most frequently prescribed anti-influenza drug (48%), followed by oseltamivir (36%), while in 2018, the newly introduced baloxavir accounted for 40.8% of prescriptions. After the emergence of COVID-19, the estimated number of patients prescribed anti-influenza drugs in 2020 dropped to just 14,000. In 2018, 37.6% of prescriptions were for patients aged < 20 years compared with 12.2% for those aged ≥ 65 years. Prescriptions for inpatients accounted for 1.1%, and the proportion of prescriptions for inpatients increased with age, with men were more likely than women to be prescribed anti-influenza drugs while hospitalized.
CONCLUSIONS
Based on our clarification of how influenza is clinically managed in Japan, future work should evaluate the clinical and economic aspects of proactively prescribing anti-influenza drugs.
Topics: Male; Humans; Female; Retrospective Studies; Influenza, Human; Japan; Prescriptions; Insurance, Health
PubMed: 37792686
DOI: 10.1371/journal.pone.0291673 -
International Journal of Antimicrobial... Apr 2024Oseltamivir is a low-cost antiviral agent that could support or complement treatment of COVID-19. This study assessed whether oseltamivir is effective in reducing...
BACKGROUND
Oseltamivir is a low-cost antiviral agent that could support or complement treatment of COVID-19. This study assessed whether oseltamivir is effective in reducing COVID-19-related mortality.
METHODS
This retrospective cohort study evaluated real-world data from a nationwide database of hospitalisation due to severe acute respiratory syndrome in Brazil. Propensity score matching was used to mimic a randomised controlled trial with 'oseltamivir' and 'no antivirals at all' as the intervention and control groups, respectively.
RESULTS
A total of 21 480 and 268 486 patients admitted between February 2020 and January 2023 were included in the intervention and control groups, respectively. After matching, the odds ratio (OR) for death was 0.901 (95% confidence interval [CI] 0.873-0.930). The OR (95% CI) for death in patients who were admitted to the ICU, and on non-invasive or invasive ventilation was 0.868 (0.821-0.917), 0.935 (0.893-0.980), and 0.883 (0.814-0.958), respectively.
CONCLUSIONS
Overall, the use of oseltamivir was associated with an attributable risk reduction of 2.50% (95% CI 1.77-3.29). Similar results were observed in patients who were admitted to the ICU, and on non-invasive or invasive ventilation. Oseltamivir is a low-cost potential antiviral treatment for COVID-19.
Topics: Humans; Antiviral Agents; COVID-19; Hospital Mortality; Oseltamivir; Retrospective Studies; Randomized Controlled Trials as Topic
PubMed: 38354825
DOI: 10.1016/j.ijantimicag.2024.107111 -
BMC Infectious Diseases Sep 2023To study the efficacy and safety of arbidol hydrochloride tablets as a treatment for influenza-like diseases. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To study the efficacy and safety of arbidol hydrochloride tablets as a treatment for influenza-like diseases.
METHODS
In this multicenter, randomized, controlled, open label study, a total of 412 influenza-like cases were collected from 14 hospitals in seven regions of Hebei Province from September 2021 to March 2022. Patients were randomly divided into two groups. The control group (n = 207) were administered oseltamivir phosphate capsules for five days and the experimental group (n = 205) were administered arbidol hydrochloride tablets for five days. The primary endpoint was the time to normal body temperature, and the secondary endpoints included the time to remission of influenza symptoms, incidence of influenza-like complications, and incidence of adverse reactions.
RESULTS
Before treatment, there was no significant difference between the two groups in general conditions, blood routine, body temperature, or symptom severity. After treatment, there was no significant difference between the groups in the mean time to fever remission (59.24 h ± 25.21 vs. 61.05 h ± 29.47) or the mean time to remission of influenza symptoms (57.31 h ± 30.19 vs. 62.02 h ± 32.08). Survival analyses using Log-rank and Wilcoxon bilateral tests showed that there was no significant difference in fever relief time or influenza symptom relief time between the two groups. Regarding the incidence of complications and adverse events, there was only one case of tracheitis, one case of nausea, one case of vomiting, and one case of dizziness in the control group. In the experimental group, there was one case of nausea, one case of vomiting, and one case of drowsiness. In addition, one patient in the control group was hospitalized for urinary calculi.
CONCLUSION
There was no significant difference between the patients with influenza-like cases treated with arbidol hydrochloride tablets and those treated with oseltamivir phosphate capsules. Further, the patients treated with arbidol hydrochloride tablets had fewer adverse reactions, and thus, the tablets were safe to use.
Topics: Humans; Capsules; Influenza, Human; Oseltamivir; Fever; Nausea; Tablets; Phosphates
PubMed: 37674112
DOI: 10.1186/s12879-023-08570-9 -
Cell Reports Mar 2024Pneumolysin (Ply) is an indispensable cholesterol-dependent cytolysin for pneumococcal infection. Although Ply-induced disruption of pneumococci-containing endosomal...
Pneumolysin (Ply) is an indispensable cholesterol-dependent cytolysin for pneumococcal infection. Although Ply-induced disruption of pneumococci-containing endosomal vesicles is a prerequisite for the evasion of endolysosomal bacterial clearance, its potent activity can be a double-edged sword, having a detrimental effect on bacterial survivability by inducing severe endosomal disruption, bactericidal autophagy, and scaffold epithelial cell death. Thus, Ply activity must be maintained at optimal levels. We develop a highly sensitive assay to monitor endosomal disruption using NanoBiT-Nanobody, which shows that the pneumococcal sialidase NanA can fine-tune Ply activity by trimming sialic acid from cell-membrane-bound glycans. In addition, oseltamivir, an influenza A virus sialidase inhibitor, promotes Ply-induced endosomal disruption and cytotoxicity by inhibiting NanA activity in vitro and greater tissue damage and bacterial clearance in vivo. Our findings provide a foundation for innovative therapeutic strategies for severe pneumococcal infections by exploiting the duality of Ply activity.
Topics: Humans; Neuraminidase; Streptococcus pneumoniae; Streptolysins; Pneumococcal Infections; Bacterial Proteins
PubMed: 38483905
DOI: 10.1016/j.celrep.2024.113962 -
Frontiers in Oncology 2024Mounting evidence has revealed the anti-cancer activity of various anti-viral drugs. Oseltamivir phosphate (OP), namely Tamiflu, is routinely used to combat influenza...
PURPOSE
Mounting evidence has revealed the anti-cancer activity of various anti-viral drugs. Oseltamivir phosphate (OP), namely Tamiflu, is routinely used to combat influenza infections. Although evidence has indicated the anti-cancer effects of OP and , little information is known about the effect of OP use on cancers in humans.
METHODS
A nationwide population-based cohort study involving 13,977,101 cases with 284,733 receiving OP was performed to examine the association between OP use and cancers using the National Health Insurance Research Database in Taiwan between 2009 and 2018.
RESULTS
The cohort study found that OP users showed a significantly lower incidence of lung cancer, colon cancer, liver, and intrahepatic bile duct cancer, oral cancer, pancreas cancer, esophagus cancer, stomach cancer, and prostate cancer. Additionally, OP users exhibited a lower risk of cancer-related mortality (adjusted HR=0.779; 95% confidence interval [CI] 0.743-0.817; p<0.001) and a reduced risk of developing liver cancer (adjusted HR=0.895; 95% CI 0.824-0.972; p=0.008), esophagus cancer (adjusted HR=0.646; 95% CI 0.522-0.799; p<0.001) and oral cancer (adjusted HR=0.587; 95% CI 0.346-0.995; p=0.048). Notably, OP users had a significant reduction in liver cancer occurrence over a 10-year period follow-up and a lower cancer stage at liver cancer diagnosis.
CONCLUSION
These findings first suggest the beneficial effects and therapeutic potential of OP use for certain cancers, especially liver cancer.
PubMed: 38469236
DOI: 10.3389/fonc.2024.1329986 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... Aug 2023This study aimed to evaluate the cost-effectiveness of Chaiyin Granules compared with Oseltamivir Phosphate Capsules in the treatment of influenza(exogenous wind-heat... (Randomized Controlled Trial)
Randomized Controlled Trial
This study aimed to evaluate the cost-effectiveness of Chaiyin Granules compared with Oseltamivir Phosphate Capsules in the treatment of influenza(exogenous wind-heat syndrome). Based on a randomized, double-blind, positive drug parallel control clinical trial, this study evaluated the pharmacoeconomics of Chaiyin Granules with cost-effectiveness analysis method. A total of 116 patients with influenza from eight hospitals(grade Ⅱ level A above) in 6 cities were selected in this study, including 78 cases in the experimental group with Chaiyin Granules and Oseltamivir Phosphate Capsules placebo, and 38 cases in the control group with Oseltamivir Phosphate Capsules and Chaiyin Granules placebo. The total cost of this study included direct medical cost, direct non-medical cost, and indirect cost. The remission time of clinical symptoms, cure time/cure rate, antipyretic onset time/complete antipyretic time, viral nucleic acid negative rate, and traditional Chinese medicine(TCM) syndrome curative effect were selected as the effect indicators for cost-effectiveness analysis. Four-quadrant diagram was used to estimate the incremental cost-effectiveness ratio. The results showed that Chaiyin Granules were not inferior to Oseltamivir Phosphate Capsules in the remission time of clinical symptoms of influenza(3.1 d vs 2.9 d, P=0.360, non-inferiority margin was 0.5 d). Compared with Oseltamivir Phosphate Capsules, Chaiyin Granules would delay the remission time of clinic symptoms of influenza for 1 d, but could save 213.9 yuan. 1 d delay in cure time could save 149.3 yuan; 1% reduction in the cure rate could save 8.2 yuan; 1 d delay in antipyretic onset time could save 295.4 yuan; 1 d delay in complete antipyretic time could save 114.3 yuan; 1% reduction in the 5-day cure rate of TCM syndrome could save 19.2 yuan. Different from other indicators, there was no statistically significant difference between two groups in the effect of negative conversion rate of viral nucleic acid, but the cost was lower and the effect was superior, and the pharmacoeconomics was not different from that of Oseltamivir Phosphate Capsules in the field of influenza treatment.
Topics: Humans; Antipyretics; Antiviral Agents; Cost-Effectiveness Analysis; Influenza, Human; Nucleic Acids; Oseltamivir; Phosphates; Treatment Outcome; Double-Blind Method
PubMed: 37802879
DOI: 10.19540/j.cnki.cjcmm.20230323.501 -
Bioorganic & Medicinal Chemistry Letters Jun 2024Neuraminidase (NA) serves as a promising target for the exploration and development of anti-influenza drugs. In this work, lead compound 5 was discovered through...
Neuraminidase (NA) serves as a promising target for the exploration and development of anti-influenza drugs. In this work, lead compound 5 was discovered through pharmacophore-based virtual screening and molecular dynamics simulation, and 14 new compounds were obtained by modifying the lead compound 5 based on pharmacophore features. The biological activity test shows that 5n (IC = 0.13 μM) has a better inhibitory effect on wild-type NA (H5N1), while 5i (IC = 0.44 μM) has a prominent inhibitory effect on mutant NA (H5N1-H274Y), both of them are better than the positive control oseltamivir carboxylate (OSC). The analysis of docking results indicate that the good activities of compounds 5n and 5i may be attributed to the thiophene ring in 5n can stretch into the 150-cavity of NA, whereas the thiophene moiety in 5i can extend to the 430-cavity of NA. The findings of this study may be helpful for the discovery of new NA inhibitors.
Topics: Neuraminidase; Enzyme Inhibitors; Antiviral Agents; Structure-Activity Relationship; Hydrazones; Influenza A Virus, H5N1 Subtype; Drug Discovery; Molecular Docking Simulation; Molecular Structure; Humans; Molecular Dynamics Simulation; Dose-Response Relationship, Drug
PubMed: 38608962
DOI: 10.1016/j.bmcl.2024.129743 -
The Journal of Infectious Diseases May 2024To gain insight into interactions among respiratory viruses, we modeled influenza A virus (IAV)-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coinfections...
To gain insight into interactions among respiratory viruses, we modeled influenza A virus (IAV)-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coinfections using differentiated human airway epithelial cultures. Replicating IAV induced a more robust interferon response than SARS-CoV-2 and suppressed SARS-CoV-2 replication in both sequential and simultaneous infections, whereas SARS-CoV-2 did not enhance host cell defense during influenza infection or suppress IAV replication. Oseltamivir, an antiviral targeting influenza, reduced IAV replication during coinfection but also reduced the host antiviral response and restored SARS-CoV-2 replication. These results demonstrate how perturbations in one viral infection can impact its effect on a coinfecting virus.
Topics: Humans; Oseltamivir; SARS-CoV-2; Antiviral Agents; Coinfection; Influenza A virus; Virus Replication; COVID-19; Influenza, Human; Viral Interference; Epithelial Cells; Respiratory Mucosa; COVID-19 Drug Treatment
PubMed: 37722683
DOI: 10.1093/infdis/jiad402