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Saudi Journal of Biological Sciences Jul 2024Still, there is no cure for the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused coronavirus disease 2019 (COVID19). The COVID19... (Review)
Review
Still, there is no cure for the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused coronavirus disease 2019 (COVID19). The COVID19 pandemic caused health emergencies which resulted in enormous medical and financial consequences worldwide including Saudi Arabia. Saudi Arabia is the largest Arab country of the Middle East. The urban setting of Saudi Arabia makes it vulnerable towards SARS-CoV-2 (SCV-2). Religious areas of this country are visited by millions of pilgrims every year for the Umrah and Hajj pilgrimage, which contributes to the potential COVID19 epidemic risk. COVID19 throws various challenges to healthcare professionals to choose the right drugs or therapy in clinical settings because of the lack of availability of newer drugs. Current drug development and discovery is an expensive, complex, and long process, which involves a high failure rate in clinical trials. While repurposing of United States Food and Drug Administration (US FDA)-approved antiviral drugs offers numerous benefits including complete pharmacokinetic and safety profiles, which significantly shorten drug development cycles and reduce costs. A range of repurposed US FDA-approved antiviral drugs including ribavirin, lopinavir/ritonavir combination, oseltamivir, darunavir, remdesivir, nirmatrelvir/ritonavir combination, and molnupiravir showed encouraging results in clinical trials in COVID19 treatment. In this article, several COVID19-related discussions have been provided including emerging variants of concern of, COVID19 pathogenesis, COVID19 pandemic scenario in Saudi Arabia, drug repurposing strategies against SCV-2, as well as repurposing of US FDA-approved antiviral drugs that might be considered to combat SCV-2 in Saudi Arabia. Moreover, drug repurposing in the context of COVID19 management along with its limitations and future perspectives have been summarized.
PubMed: 38799719
DOI: 10.1016/j.sjbs.2024.104023 -
Communicable Diseases Intelligence... Jul 2023As part of its role in the World Health Organization's (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and...
As part of its role in the World Health Organization's (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received a record total of 12,073 human influenza positive samples during 2022. Viruses were analysed for their antigenic, genetic and antiviral susceptibility properties. Selected viruses were propagated in qualified cells or embryonated hen's eggs for potential use in seasonal influenza virus vaccines. In 2022, influenza A(H3N2) viruses predominated over influenza A(H1N1)pdm09 and B viruses, accounting for 77% of all viruses analysed. The majority of A(H1N1)pdm09, A(H3N2) and influenza B viruses analysed at the Centre were found to be antigenically and genetically similar to the respective WHO recommended vaccine strains for the southern hemisphere in 2022. Of 3,372 samples tested for susceptibility to the neuraminidase inhibitors oseltamivir and zanamivir, two A(H1N1)pdm09 viruses showed highly reduced inhibition against oseltamivir.
Topics: Animals; Female; Humans; Australia; Chickens; Drug Resistance, Viral; Influenza A virus; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza Vaccines; Influenza, Human; Oseltamivir; World Health Organization; Zanamivir; Antiviral Agents
PubMed: 37817300
DOI: 10.33321/cdi.2023.47.43 -
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 -
Molecules (Basel, Switzerland) Sep 2023Influenza represents a profoundly transmissible viral ailment primarily afflicting the respiratory system. Neuraminidase inhibitors constitute a class of antiviral...
Influenza represents a profoundly transmissible viral ailment primarily afflicting the respiratory system. Neuraminidase inhibitors constitute a class of antiviral therapeutics employed in the management of influenza. These inhibitors impede the liberation of the viral neuraminidase protein, thereby impeding viral dissemination from the infected cell to host cells. As such, neuraminidase has emerged as a pivotal target for mitigating influenza and its associated complications. Here, we apply a de novo hybridization approach based on a breed-centric methodology to elucidate novel neuraminidase inhibitors. The breed technique amalgamates established ligand frameworks with the shared target, neuraminidase, resulting in innovative inhibitor constructs. Molecular docking analysis revealed that the seven synthesized breed molecules (designated Breeds 1-7) formed more robust complexes with the neuraminidase receptor than conventional clinical neuraminidase inhibitors such as zanamivir, oseltamivir, and peramivir. Pharmacokinetic evaluations of the seven breed molecules (Breeds 1-7) demonstrated favorable bioavailability and optimal permeability, all falling within the specified parameters for human application. Molecular dynamics simulations spanning 100 nanoseconds corroborated the stability of these breed molecules within the active site of neuraminidase, shedding light on their structural dynamics. Binding energy assessments, which were conducted through MM-PBSA analysis, substantiated the enduring complexes formed by the seven types of molecules and the neuraminidase receptor. Last, the investigation employed a reaction-based enumeration technique to ascertain the synthetic pathways for the synthesis of the seven breed molecules.
Topics: Humans; Neuraminidase; Influenza, Human; Molecular Docking Simulation; Hybridization, Genetic; Antiviral Agents; Enzyme Inhibitors; Central Nervous System Depressants
PubMed: 37764457
DOI: 10.3390/molecules28186678 -
The Science of the Total Environment Jul 2023The COVID-19 pandemic resulted in unprecedented usage and elevated environmental concentrations of antiviral drugs. However, very limited studies have reported their...
The COVID-19 pandemic resulted in unprecedented usage and elevated environmental concentrations of antiviral drugs. However, very limited studies have reported their sorption characteristics on environmental matrices. This study investigated the sorption of six COVID-19 related antivirals on Taihu Lake sediment with varied aqueous chemistry. Results showed that the sorption isotherms for arbidol (ABD), oseltamivir (OTV), and ritonavir (RTV) were linear, while the Freundlich model was the best-fit for ribavirin (RBV) and the Langmuir model for favipiravir (FPV) and remdesivir (RDV). Their distribution coefficient, K varied between 5.051 L/kg to 248.6 L/kg with the sorption capacities ranked as FPV > RDV > ABD > RTV > OTV > RBV. Alkaline conditions (pH 9) and elevated cation strength (0.05 M to 0.1 M) decreased the sorption capacities of the sediment for these drugs. Thermodynamic analysis revealed that the spontaneous sorption of RDV, ABD, and RTV was between physisorption and chemisorption while FPV, RBV, and OTV were mainly physisorption. Functional groups related to hydrogen bonds, π - π interaction, and surface complexation were implicated in the sorption processes. These findings enhance our understanding about the environmental fate of COVID-19 related antivirals and provide basic data for predicting their distribution and risk in the environment.
Topics: Humans; Antiviral Agents; Geologic Sediments; Pandemics; COVID-19; Ritonavir; Oseltamivir; Adsorption
PubMed: 37120016
DOI: 10.1016/j.scitotenv.2023.163736 -
Revista Paulista de Pediatria : Orgao... 2023To evaluate severe acute respiratory syndrome surveillance in a pediatric unit.
OBJECTIVE
To evaluate severe acute respiratory syndrome surveillance in a pediatric unit.
METHODS
Descriptive study of reported severe acute respiratory syndrome cases with the detection of respiratory viruses in the nasopharyngeal sample of patients hospitalized between 2013 and 2019, in a reference hospital in the Federal District, Brazil.
RESULTS
A total of 269 children had one or more viruses detected, resulting in 280 viruses, of which 152 (54%) were respiratory syncytial virus. The detection of respiratory syncytial virus was higher during the autumn-winter period. Children´s median age was 6.9 months, 156 (58%) were male, 104 (39%) had comorbidity, 197 (73%) required mechanical ventilation, 241 (90%) received antibiotics, and 146 (54%) oseltamivir. There were 19 (7%) deaths. The median time from symptom onset to sample collection was 5 days and the median time from sample collection to final results was 6 days.
CONCLUSIONS
The system needs to reduce the time to deliver results so that inappropriate use of antibiotics and antivirals can be avoided. Moreover, the burden of viral pneumonia was relevant and the system must be flexible enough to include emerging viruses in order to be useful in responding to public health emergencies caused by respiratory viruses.
Topics: Child; Humans; Male; Infant; Female; Antiviral Agents; Respiratory Syncytial Viruses; Pneumonia, Viral; Oseltamivir; Anti-Bacterial Agents
PubMed: 37646750
DOI: 10.1590/1984-0462/2024/42/2022215 -
ACS Omega Dec 2023Influenza remains one of the most widespread infections, causing an annual illness in adults and children. Therefore, the search for new antiviral drugs is one of the...
Influenza remains one of the most widespread infections, causing an annual illness in adults and children. Therefore, the search for new antiviral drugs is one of the priorities of practical health care. Eight isorhamnetin glycosides were purified from Persicaria species, characterized by nuclear magnetic resonance spectroscopy and mass spectrometry and then evaluated as potential agents against influenza virus. A comprehensive in vitro and in vivo assessment of the compounds revealed that compound 5 displayed the most potent inhibitory activity with an EC value of 1.2-1.3 μM, better than standard drugs (isorhamnetin 28.0-56.0 μM and oseltamivir 1.3-9.1 μM). Molecular docking results also revealed that compound 5 has the lowest binding energy (-10.7 kcal/mol) among the tested compounds and isorhamnetin (-8.1 kcal/mol). The ability of the isorhamnetin glycosides to suppress the reproduction of the influenza virus was studied on a model of a cell culture and chicken embryos. The ability of active compounds to influence the structure of the virion, as well as the activity of hemagglutinin and neuraminidase, has been demonstrated. Compound 1, 5, and 6 demonstrated the most effective inhibition of virus replication for all tested viruses. Molecular dynamics simulation techniques were run for 100 ns for compound 5 with two protein receptors Hem (1RUY) and Neu (3BEQ). These results revealed that the Hem-complex system acquired a relatively more stable conformation and even better descriptors than the other Neu-complex studied systems, suggesting that it can be an effective inhibiting drug toward hemagglutinin than neuraminidase inhibition. Based on the reported results, compound 5 can be a good candidate to be evaluated for effectiveness in preclinical testing.
PubMed: 38144046
DOI: 10.1021/acsomega.3c08407 -
Microorganisms May 2024Both pandemic and seasonal influenza are major health concerns, causing significant mortality and morbidity. Current influenza drugs primarily target viral neuraminidase...
Both pandemic and seasonal influenza are major health concerns, causing significant mortality and morbidity. Current influenza drugs primarily target viral neuraminidase and RNA polymerase, which are prone to drug resistance. Polyoxometalates (POMs) are metal cation clusters bridged by oxide anions. They have exhibited potent anti-tumor, antiviral, and antibacterial effects. They have remarkable activity against various DNA and RNA viruses, including human immunodeficiency virus, herpes simplex virus, hepatitis B and C viruses, dengue virus, and influenza virus. In this study, we have identified sodium polyoxotungstate (POM-1) from an ion channel inhibitor library. In vitro, POM-1 has been demonstrated to have potent antiviral activity against H1N1, H3N2, and oseltamivir-resistant H1N1 strains. POM-1 can cause virion aggregation during adsorption, as well as endocytosis. However, the aggregation is reversible; it does not interfere with virus adsorption and endocytosis. Our results suggest that POM-1 exerts its antiviral activity by inhibiting the nuclear import of viral ribonucleoprotein (vRNP). This distinct mechanism of action, combined with its wide range of efficacy, positions POM-1 as a promising therapeutic candidate for influenza treatment and warrants further investigation.
PubMed: 38792846
DOI: 10.3390/microorganisms12051017 -
Biomedicine & Pharmacotherapy =... Apr 2024Sphingolipid transporter 1 (SPNS1) is a significant differentially expressed gene (DEGs) in esophageal squamous cell carcinoma (ESCC). According to 3 pairs clinic...
Sphingolipid transporter 1 (SPNS1) is a significant differentially expressed gene (DEGs) in esophageal squamous cell carcinoma (ESCC). According to 3 pairs clinic cohorts, transcriptomic (155 pairs of ESCC samples and GSE53624, and proteomic data from PXD021701 including 124 ESCC samples) we found that SPNS1 was significantly higher in ESCC tissues compared to adjacent normal esophagus tissues. ESCC patients with high SPNS1 had a significantly poorer clinical prognosis than those with low SPNS1. Knockdown of SPNS1 significantly inhibited the proliferation, migration, and invasion abilities of ESCC cells, while promoting apoptosis. And overexpression of SPNS1 exhibited opposite functions. Furthermore, ESCC cells became more sensitive to 5-fluorouracil (5-FU) when SPNS1 was knocked down. Transcriptome sequencing revealed that NEU1 was one significant DEG affected by SPNS1 and positively correlated with SPNS1 expression. Oseltamivir phosphate (OP), one NEU1 inhibitor, markedly reversed 5-FU resistance, migration, and proliferation induced by high expression of SPNS1 both in vivo and in vitro. Our findings indicated that SPNS1 might promote the progression of ESCC by upregulating NEU1 expression and influencing chemotherapy sensitivity. These results provide new perceptions into potential therapeutic targets for ESCC treatment. The present study aimed to investigate the role and underlying mechanism of SPNS1 in ESCC.
Topics: Humans; Esophageal Squamous Cell Carcinoma; Oseltamivir; Esophageal Neoplasms; Proteomics; Cell Line, Tumor; Cell Proliferation; Fluorouracil; Cell Movement; Gene Expression Regulation, Neoplastic
PubMed: 38460365
DOI: 10.1016/j.biopha.2024.116367 -
Cureus Dec 2023Pulmonary embolisms (PEs) are potentially life-threatening emergencies that carry significant morbidity and mortality. Advances in treatment options and the safety of...
Pulmonary embolisms (PEs) are potentially life-threatening emergencies that carry significant morbidity and mortality. Advances in treatment options and the safety of existing procedures have effectively reduced the long-term and short-term effects of the condition. Therefore, it is important to make an early diagnosis so that treatment options can be thoroughly explored. The D-dimer is an important tool in the early diagnosis of PEs. It is especially useful in ruling out the diagnosis in patients with a low to moderate suspicion of the disease. We present a case of a 22-year-old male who presented with exertional dyspnea, congestion, and rhinorrhea for one day and was noted to have persistent hypoxia and tachycardia. The influenza test was positive, and he was started on oseltamivir. Due to persistent hypoxia, a CT pulmonary angiogram was ordered and revealed filling defects in the left lower lobe segmental vessels suggestive of PE, as well as multifocal multilobar bilateral ground-glass opacities. He was initially treated with a heparin drip and subsequently switched to eliquis. After a significant improvement in his hypoxia, he was discharged home for outpatient follow-up, including a hypercoagulable workup. This case demonstrates that despite the usefulness of the D-dimer as a diagnostic tool for PEs, it cannot solely or fully replace the full gamut of screening tools used to determine the risk of PE. Although rare, false-negative scores do occur; therefore, the tool should always be used in conjunction with other scoring systems, physician gestalt, and within the specific clinical context.
PubMed: 38264382
DOI: 10.7759/cureus.51045