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Journal of Neurovirology Feb 2021As the SARS-COV-2 becomes a global pandemic, many researchers have a concern about the long COVID-19 complications. Chronic fatigue syndrome/myalgic encephalomyelitis...
As the SARS-COV-2 becomes a global pandemic, many researchers have a concern about the long COVID-19 complications. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a persistent, debilitating, and unexplained fatigue disorder. We investigated psychological morbidities such as CFS and post-traumatic stress disorder (PTSD) among survivors of COVID-19 over 6 months. All COVID-19 survivors from the university-affiliated hospital of Tehran, Iran, were assessed 6 months after infection onset by a previously validated questionnaire based on the Fukuda guidelines for CFS/EM and DSM-5 Checklist for PTSD (The Post-traumatic Stress Disorder Checklist for DSM-5 or PCL-5) to determine the presence of stress disorder and chronic fatigue problems. A total of 120 patients were enrolled. The prevalence rate of fatigue symptoms was 17.5%. Twelve (10%) screened positive for chronic idiopathic fatigue (CIF), 6 (5%) for CFS-like with insufficient fatigue syndrome (CFSWIFS), and 3 (2.5%) for CFS. The mean total scores in PCL-5 were 9.27 ± 10.76 (range:0-44), and the prevalence rate of PTSD was 5.8%. There was no significant association after adjusting between CFS and PTSD, gender, comorbidities, and chloroquine phosphate administration. The obtained data revealed the prevalence of CFS among patients with COVID-19, which is almost similar to CFS prevalence in the general population. Moreover, PTSD in patients with COVID-19 is not associated with the increased risk of CFS. Our study suggested that medical institutions should pay attention to the psychological consequences of the COVID-19 outbreak.
Topics: Adult; Aged; Antiviral Agents; COVID-19; Cough; Dementia; Drug Combinations; Dyspnea; Fatigue Syndrome, Chronic; Female; Fever; Humans; Hydroxychloroquine; Lopinavir; Male; Middle Aged; Oseltamivir; Research Design; Ritonavir; SARS-CoV-2; Severity of Illness Index; Stress Disorders, Post-Traumatic; Surveys and Questionnaires; Survivors; COVID-19 Drug Treatment
PubMed: 33528827
DOI: 10.1007/s13365-021-00949-1 -
The Journal of Antimicrobial... Jan 2021Baloxavir acid, the active form of the orally available prodrug baloxavir marboxil, is a novel cap-dependent endonuclease inhibitor of influenza virus. Baloxavir...
BACKGROUND
Baloxavir acid, the active form of the orally available prodrug baloxavir marboxil, is a novel cap-dependent endonuclease inhibitor of influenza virus. Baloxavir marboxil has been shown to rapidly reduce virus titres compared with oseltamivir in clinical studies.
OBJECTIVES
We investigated the relationship between pharmacokinetic (PK) parameters and antiviral activity of baloxavir acid based on virus titre reduction in lungs of infected mice.
METHODS
BALB/c mice infected with a sub-lethal dose of influenza A(H1N1), A(H1N1)pdm09, A(H3N2) or type B virus were treated on day 5 with oral baloxavir marboxil (0.5-50 mg/kg q12h), subcutaneous baloxavir acid (0.25-8 mg/kg/day), oseltamivir phosphate (5 or 50 eq mg/kg q12h) or other antivirals for 1 day. Lung virus titres were assessed 24 h after initial antiviral dosing. PK testing was performed at up to 24 h post-dosing of baloxavir marboxil or baloxavir acid in A/WSN/33-infected mice and the PK/pharmacodynamic (PD) relationship was evaluated for baloxavir acid.
RESULTS
Oral baloxavir marboxil administration showed dose-dependent virus titre reductions in lungs of mice infected with the different types/subtypes of influenza viruses 24 h post-dosing. Baloxavir marboxil at 15 mg/kg q12h resulted in ≥100-fold and ≥10-fold reductions in influenza A and B virus titres, respectively, compared with oseltamivir phosphate. PK/PD analysis showed that the plasma concentration at the end of the dosing interval (Cτ) or the plasma concentration at 24 h after initial dosing (C24) was the PK parameter predicting the virus titres at 24 h post-dosing of baloxavir acid.
CONCLUSIONS
PK/PD analysis of baloxavir acid based on virus titre reduction in this mouse model could be helpful in predicting and maximizing virological outcomes in clinical settings.
Topics: Animals; Antiviral Agents; Dibenzothiepins; Disease Models, Animal; Endonucleases; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza, Human; Mice; Mice, Inbred BALB C; Morpholines; Oxazines; Pyridones; Triazines
PubMed: 33035324
DOI: 10.1093/jac/dkaa393 -
Journal of the American Chemical Society Aug 2018We herein report a gram-scale, enantioselective synthesis of Tamiflu, in which the key trans-diamino moiety has been efficiently installed via an iron-catalyzed...
We herein report a gram-scale, enantioselective synthesis of Tamiflu, in which the key trans-diamino moiety has been efficiently installed via an iron-catalyzed stereoselective olefin diazidation. This significantly improved, iron-catalyzed method is uniquely effective for highly functionalized yet electronically deactivated substrates that have been previously problematic. Preliminary catalyst structure-reactivity-stereoselectivity relationship studies revealed that both the iron catalyst and the complex substrate cooperatively modulate the stereoselectivity for diazidation. Safety assessment using both differential scanning calorimetry (DSC) and the drop weight test (DWT) has also demonstrated the feasibility of carrying out this iron-catalyzed olefin diazidation for large-scale Tamiflu synthesis.
Topics: Alkenes; Antiviral Agents; Azides; Calorimetry, Differential Scanning; Catalysis; Iron; Oseltamivir; Stereoisomerism
PubMed: 30040881
DOI: 10.1021/jacs.8b06900 -
The American Journal of Case Reports Jun 2018BACKGROUND Tamiflu (oseltamivir phosphate) serves as prophylaxis and treatment of upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI)...
BACKGROUND Tamiflu (oseltamivir phosphate) serves as prophylaxis and treatment of upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI) caused by viruses of the Orthomyxovirus family. Here, we present a patient with URTI and negative rapid influenza diagnostic testing (RIDT), who developed rhabdomyolysis after being started on oseltamivir. CASE REPORT Our report describes a rare case of rhabdomyolysis after oseltamivir administration in a 53-year-old man with suspected influenza. We discuss the differential diagnosis for rhabdomyolysis to rule out other causes and review the literature on influenza-induced rhabdomyolysis. CONCLUSIONS Considering the serious consequences of rhabdomyolysis, care needs to be taken in routine prescription and use of oseltamivir. Although this is a rare adverse effect, our case highlights the need to be vigilant for uncommon adverse events with commonly used drugs.
Topics: Antiviral Agents; Humans; Influenza, Human; Male; Middle Aged; Oseltamivir; Rhabdomyolysis
PubMed: 29887593
DOI: 10.12659/AJCR.909278 -
Clinical & Translational Immunology 2023Novel host-targeted therapeutics could treat severe influenza A virus (IAV) infections, with reduced risk of drug resistance. LAT8881 is a synthetic form of the...
OBJECTIVES
Novel host-targeted therapeutics could treat severe influenza A virus (IAV) infections, with reduced risk of drug resistance. LAT8881 is a synthetic form of the naturally occurring C-terminal fragment of human growth hormone. Acting independently of the growth hormone receptor, it can reduce inflammation-induced damage and promote tissue repair in an animal model of osteoarthritis. LAT8881 has been assessed in clinical trials for the treatment of obesity and neuropathy and has an excellent safety profile. We investigated the potential for LAT8881, its metabolite LAT9991F and LAT7771 derived from prolactin, a growth hormone structural homologue, to treat severe IAV infection.
METHODS
LAT8881, LAT9991F and LAT7771 were evaluated for their effects on cell viability and IAV replication , as well as their potential to limit disease in a preclinical mouse model of severe IAV infection.
RESULTS
LAT8881 treatment enhanced cell viability, particularly in the presence of cytotoxic stress, which was countered by siRNA inhibition of host lanthionine synthetase C-like proteins. Daily intranasal treatment of mice with LAT8881 or LAT9991F, but not LAT7771, from day 1 postinfection significantly improved influenza disease resistance, which was associated with reduced infectious viral loads, reduced pro-inflammatory cytokines and increased abundance of protective alveolar macrophages. LAT8881 treatment in combination with the antiviral oseltamivir phosphate led to more pronounced reduction in markers of disease severity than treatment with either compound alone.
CONCLUSION
These studies provide the first evidence identifying LAT8881 and LAT9991F as novel host-protective therapies that improve survival, limit viral replication, reduce local inflammation and curtail tissue damage during severe IAV infection. Evaluation of LAT8881 and LAT9991F in other infectious and inflammatory conditions of the airways is warranted.
PubMed: 36969366
DOI: 10.1002/cti2.1443 -
PloS One 2020Glycosphingolipids (GSLs) hexosylceramides and lactosylceramides are elevated in lupus mice and human patients with nephritis. Whereas other renal diseases characterized...
Glycosphingolipids (GSLs) hexosylceramides and lactosylceramides are elevated in lupus mice and human patients with nephritis. Whereas other renal diseases characterized by increased GSL levels are thought to be a result of upregulated GSL synthesis, our results suggest elevated hexosylceramides and lactosylceramides in lupus nephritis is a result of increased catabolism of ganglioside GM3 due to significantly increased neuraminidase (NEU) activity. Thus, we hypothesized GM3 would be decreased in lupus nephritis kidneys and blocking NEU activity would reduce GSLs and improve disease in lupus mice. Female MRL/lpr lupus mice were treated with water or the NEU inhibitor oseltamivir phosphate at the onset of proteinuria to block GSL catabolism. Age-matched (non-nephritic) female MRL/MpJ lupus mice served as controls. Renal GM3 levels were significantly higher in the nephritic MRL/lpr water-treated mice compared to non-nephritic MRL/MpJ mice, despite significantly increased renal NEU activity. Blocking GSL catabolism increased, rather than decreased, renal and urine GSL levels and disease was not significantly impacted. A pilot study treating MRL/lpr females with GlcCer synthase inhibitor Genz-667161 to block GSL synthesis resulted in a strong significant negative correlation between Genz-667161 dose and renal GSL hexosylceramide and GM3 levels. Splenomegaly was negatively correlated and serum IgG levels were marginally correlated with increasing Genz-667161 dose. These results suggest accumulation of renal GM3 may be due to dysregulation of one or more of the GSL ganglioside pathways and inhibiting GSL synthesis, but not catabolism, may be a therapeutic approach for treating lupus nephritis.
Topics: Animals; Ceramides; Female; G(M3) Ganglioside; Glycosphingolipids; Kidney; Lactosylceramides; Lupus Nephritis; Mice; Mice, Inbred MRL lpr; Neuraminidase; Oseltamivir; Phosphorous Acids; Pilot Projects; Proteinuria
PubMed: 32187230
DOI: 10.1371/journal.pone.0230499 -
World Journal of Clinical Cases Jun 2020Since December 2019, many cases of pneumonia caused by novel coronavirus have been discovered in Wuhan, China, and such cases have spread nationwide quickly. At present,...
BACKGROUND
Since December 2019, many cases of pneumonia caused by novel coronavirus have been discovered in Wuhan, China, and such cases have spread nationwide quickly. At present, coronavirus disease 2019 (COVID-19) is a worldwide pandemic. What are the clinical features of this disease? What is the clinical diagnosis and how should such patients be treated? As a clinician, mastery of the clinical characteristics, basic diagnosis, and treatment methods of COVID-19 are required to provide help to patients.
CASE SUMMARY
A 42-year-old male patient with a cough lasting 6 d without obvious cause, as well as fever and fatigue for 1 d, was admitted to Hankou Hospital on January 22, 2020 and transferred to Huoshenshan Hospital on February 4. The main clinical symptoms were dry cough, fatigue, and fever. He was diagnosed with COVID-19. From the 4 d of admission, the patient's condition gradually worsened, with increased respiratory rate and body temperature. Peripheral blood lymphocytes decreased progressively. On the 8 d of admission, the patient's highest temperature was 40.7 °C, and oxygen saturation was 83% despite high-flow oxygen inhalation. Chest computed tomography results showed that the virus progressed rapidly. The number of lesions significantly increased with expanded scope and increased density. The distribution of lesions advanced from peripheral to central. In addition to nasal catheter oxygen inhalation and symptomatic support, antiviral drugs were used throughout the treatment. On January 22, oseltamivir phosphate capsules were given orally (75 mg, twice daily) for 6 d. On January 24, three tablets of lopinavir and ritonavir were added orally (twice daily). After 6 d, this was changed to 0.2 g (two tablets) arbidol, taken orally (three times daily) for 5 d. During the severe stage, methylprednisolone was given (40 mg) once every 12 h, immunoglobulin (20 g) was administered by intravenous drip infusion once daily, and thymosin (1.6 mg) was injected subcutaneously once daily combined with immunotherapy. On February 2, symptoms decreased, various indicators improved, and pulmonary inflammation was obviously reduced. Throat swabs on February 4 and 9 were negative for novel coronavirus nucleic acid. After 19 d in the hospital, the patient was successfully treated and discharged.
CONCLUSION
COVID-19 in young adults can be successfully treated with active treatment. We report a typical case of COVID-19, analyze its clinical characteristics, summarize its clinical diagnosis and treatment experience, and provide a reference for clinical colleagues.
PubMed: 32548163
DOI: 10.12998/wjcc.v8.i11.2325 -
Alternative Therapies in Health and... Nov 2023Influenza is one of the major public health problems worldwide. Children are the high-risk group for influenza and the high-risk population with symptoms. Huashi...
Efficacy and Safety of Huashi Baidu Granules in the Treatment of Children Suffering from Influenza with Exterior-cold and Interior-heat Syndrome: A Multi-center, Randomized Controlled Trial Protocol.
BACKGROUND
Influenza is one of the major public health problems worldwide. Children are the high-risk group for influenza and the high-risk population with symptoms. Huashi Baidu(HSBD) Granules have played a great role in fighting against COVID-19. In recent decades, this recipe has also been applied by pediatricians to treat influenza, with remarkable curative effects. However, there is still a lack of high-quality evidence-based medical practice.
METHODS
This study was designed as a multi-center, randomized, parallel-controlled trial, with an estimated sample size of 520 children suffering from influenza with exterior-cold and interior-heat syndrome. All the enrolled children will be randomly assigned to a test group and a control group. Children in the test group were treated with Huashi Baidu Granules, and those in the control group were provided with Oseltamivir Phosphate Granules for intervention. The primary outcome measure was the time to clinical recovery, with the Chinese version of the Canadian Acute Respiratory Illness and Flu Scale (CARIFS) score measured at baseline and every 24 hours after treatment, which was evaluated at the endpoint of follow-up. The secondary outcome was the time to complete fever remission, scores of CARIFS symptom dimensions and the area under the curve with time, the incidence of complications/severe/critical influenza, the rate of single symptom disappearance, and the therapeutic effect of traditional Chinese medicine syndromes, which were recorded at baseline and after treatment, and evaluated at the end of treatment. Safety and endpoint events were evaluated at the same time.
CONCLUSION
This study is intended to apply Huashi Baidu Granules to treat influenza with exterior-cold and interior-heat syndrome to identify the clinical efficacy and safety of this recipe. Simultaneously, our study will also discuss the characteristics of clinical syndrome in traditional Chinese medicine and syndrome distribution of influenza in the studied children.
PubMed: 37917893
DOI: No ID Found -
Influenza and Other Respiratory Viruses Nov 2020Baloxavir marboxil (BXM), the oral prodrug of baloxavir acid (BXA), greatly reduces virus titers as well as influenza symptoms of uncomplicated influenza in patients.
BACKGROUND
Baloxavir marboxil (BXM), the oral prodrug of baloxavir acid (BXA), greatly reduces virus titers as well as influenza symptoms of uncomplicated influenza in patients.
OBJECTIVES
To investigate the pharmacokinetic profiles of BXA and its efficacy against influenza A virus infection in ferrets.
METHODS
Ferrets were dosed orally with BXM (10 and 30 mg/kg twice daily for 1 day), oseltamivir phosphate (OSP) (5 mg/kg twice daily for 2 days) or vehicle to measure the antiviral effects of BXM and OSP. The pharmacokinetic parameters of BXA was determined after single oral dosing of BXM.
RESULTS
The maximum plasma concentrations of BXA were observed at 1.50 and 2.00 hours with the two BXM doses, which then declined with an elimination half-life of 6.91 and 4.44 hours, respectively. BXM at both doses remained detectable in the plasma in ferrets, which may be due to higher stability in liver microsomes. BXM (10 and 30 mg/kg twice daily) treatment at Day 1 post-infection (p.i.) reduced virus titers by ≥3 log10 of the 50% tissue culture infective doses by Day 2, which was significantly different compared with vehicle or OSP. Body temperature drops over time were significantly greater with BXM than with vehicle or OSP. Significant reduction in virus titers was also demonstrated when BXM was administrated after symptom onset at Day 2 p.i. compared with vehicle and OSP, although body temperature changes largely overlapped between Day 2 and Day 4.
CONCLUSIONS
The results highlight the rapid antiviral action of BXM with post-exposure prophylaxis or therapeutic dosing in ferrets and offer support for further research on prevention of influenza virus infection and transmission.
Topics: Animals; Antiviral Agents; Body Temperature; Dibenzothiepins; Ferrets; Humans; Influenza A virus; Influenza, Human; Microsomes; Morpholines; Orthomyxoviridae Infections; Oseltamivir; Pyridones; Triazines; Viral Load
PubMed: 32533654
DOI: 10.1111/irv.12760 -
Mucosal Immunology Sep 2016We previously reported that TLR4(-/-) mice are refractory to mouse-adapted A/PR/8/34 (PR8) influenza-induced lethality and that therapeutic administration of the TLR4...
We previously reported that TLR4(-/-) mice are refractory to mouse-adapted A/PR/8/34 (PR8) influenza-induced lethality and that therapeutic administration of the TLR4 antagonist Eritoran blocked PR8-induced lethality and acute lung injury (ALI) when given starting 2 days post infection. Herein we extend these findings: anti-TLR4- or -TLR2-specific IgG therapy also conferred significant protection of wild-type (WT) mice from lethal PR8 infection. If treatment is initiated 3 h before PR8 infection and continued daily for 4 days, Eritoran failed to protect WT and TLR4(-/-) mice, implying that Eritoran must block a virus-induced, non-TLR4 signal that is required for protection. Mechanistically, we determined that (i) Eritoran blocks high-mobility group B1 (HMGB1)-mediated, TLR4-dependent signaling in vitro and circulating HMGB1 in vivo, and an HMGB1 inhibitor protects against PR8; (ii) Eritoran inhibits pulmonary lung edema associated with ALI; (iii) interleukin (IL)-1β contributes significantly to PR8-induced lethality, as evidenced by partial protection by IL-1 receptor antagonist (IL-1Ra) therapy. Synergistic protection against PR8-induced lethality was achieved when Eritoran and the antiviral drug oseltamivir were administered starting 4 days post infection. Eritoran treatment does not prevent development of an adaptive immune response to subsequent PR8 challenge. Overall, our data support the potential of a host-targeted therapeutic approach to influenza infection.
Topics: Acute Lung Injury; Animals; Antiviral Agents; Disaccharides; Drug Synergism; Female; Gene Expression Regulation; HMGB1 Protein; Immunity, Innate; Immunoglobulin G; Interleukin-1 Receptor Accessory Protein; Lung; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular Targeted Therapy; Orthomyxoviridae; Orthomyxoviridae Infections; Oseltamivir; Signal Transduction; Sugar Phosphates; Survival Analysis; Toll-Like Receptor 2; Toll-Like Receptor 4
PubMed: 26813341
DOI: 10.1038/mi.2015.141