Analysis of the SARS-CoV-2 nsp12 P323L/A529V mutations: coeffect in the transiently peaking lineage C.36.3 on protein structure and response to treatment in Egyptian records

Zeitschrift für Naturforschung C, Journal Year: 2024, Volume and Issue: 79(1-2), P. 13 - 24

Published: Jan. 1, 2024

Abstract SARS-CoV-2 nsp12, the RNA-dependent RNA-polymerase plays a crucial role in virus replication. Monitoring effect of its emerging mutants on viral replication and response to antiviral drugs is important. Nsp12 two Egyptian isolates circulating 2020 2021 were sequenced. Both included P323L, one A529V. Tracking A529V mutant frequency, it relates transience peaked C.36.3 variant parent C.36, both worldwide February–August 2021, enlisted as high transmissible variants under investigation (VUI) May 2021. Mutants reported originate from Egypt showed an abrupt low frequency upon screening, we analyzed all 1104 nsp12 sequences. mutation was 36 records with June As possible reappearance might obligate actions for candidate VUI, predicted co-effect P323L mutations protein stability dynamics through structure simulations. Three available structures drug–nsp12 interaction used representing remdesivir, suramin favipiravir drugs. Remdesivir increase considerable change flexibility while extreme interaction. Results predict favored efficiency except case mutations.

Language: Английский

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Treatment-Related Risk Factors for Adverse Outcomes of COVID-19 in Patients Treated for Lymphoid Malignancies in the Pre-Omicron Era—A Study of KroHem, the Croatian Group for Hematologic Diseases

Biomedicines, Journal Year: 2024, Volume and Issue: 12(2), P. 331 - 331

Published: Jan. 31, 2024

Patients with lymphoid malignancies are at increased risk of death or prolonged infection due to COVID-19. Data on the influence different antineoplastic treatment modalities outcomes conflicting. Anti-CD20 monoclonal antibodies increase infection. It is unclear whether this affected by choice antibody (rituximab vs. obinutuzumab). To elucidate role therapy COVID-19 outcomes, KroHem collected data patients diagnosed between October 2020 and April 2021. A total 314 were identified, 75 untreated, 61 off 178 treatment. The mortality rate in untreated off-treatment was 15% 16%; 9% 10% had In on-treatment group, 3% still positive time collection, 62% recovered 35% died; 42% Disease type, use anti-CD20 antibodies, prior autologous stem-cell transplantation (ASCT) line did not significantly affect mortality. Mortality higher older (p = 0.0078) those treated purine analogues 0.012). Prolonged more frequent 0.012), especially obinutuzumab, Age, ASCT These suggest that age main factors for malignancies. Obinutuzumab further increases disease, but death, comparison rituximab. Epidemiological considerations should be taken into account when choosing appropriate

Language: Английский

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Analysis of risk factors for painful diabetic peripheral neuropathy and construction of a prediction model based on Lasso regression

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 22, 2024

Objective To evaluate the prevalence and risk factors of painful diabetic peripheral neuropathy (PDPN) in patients with type 2 (DPN) Hunan Province, establish verify prediction model. Methods This was a retrospective study involving 4908 patients, all were randomly divided into training dataset(3436 cases)and validation dataset (1472 cases) ratio 7:3. Electroneurogram, clinical signs,and symptoms used to neuropathy. Least absolute shrinkage selection operator (LASSO) regression select optimal factors, multifactorial logistic analysis build Calibration plots, decision curve (DCA), subject work characteristic curves (ROC) assess predictive effects. Result The PDPN 33.2%, multivariate model showed that artery disease, duration diabetes, smoking, HBA1c independent for diabetes. ROC results AUC established 0.872 0.843 dataset. calibration show has good consistency significant net benefit. Conclusion 33.2% DPN had China. Peripheral are is based on above which can well predict probability PDPN.

Language: Английский

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Retrospective Analysis of the Effectiveness of Remdesivir in COVID-19 Treatment during Periods Dominated by Delta and Omicron SARS-CoV-2 Variants in Clinical Settings

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(6), P. 2371 - 2371

Published: March 19, 2023

Continuous evaluation of real-world treatment effectiveness COVID-19 medicines is required due to the ongoing evolution SARS-CoV-2 and possible emergence resistance. Therefore, this study aimed analyze, in a retrospective manner, outcomes patients hospitalized with during pandemic waves dominated by Delta Omicron variants treated remdesivir (RDV) (n = 762) comparison demographically clinically matched group not any antivirals 1060). A logistic regression analysis revealed that RDV was associated significantly lower risk death both wave (OR 0.42, 95%CI: 0.29-0.60; p < 0.0001) Omicron-dominated period 0.56, 0.35-0.92; 0.02). Moreover, RDV-treated groups were characterized percentage requiring mechanical ventilation, but difference statistically significant. This first evidence remains effective dominance more pathogenic those cause milder course disease, continues be an essential element therapy.

Language: Английский

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Impact of Alteplase on Mortality in Critically Ill Patients with COVID-19 and Pulmonary Embolism

Viruses, Journal Year: 2023, Volume and Issue: 15(7), P. 1513 - 1513

Published: July 7, 2023

COVID-19 is an independent risk factor for pulmonary embolism (PE). Little known about alteplase therapy in this patient group. A retrospective study analyzed 74 patients with PE and acute respiratory distress syndrome (ARDS) due to who were hospitalized the intensive care unit 2021. Patients or without confirmed right heart thrombi (RHT) treated unfractionated heparin alteplase. The mortality rate RHT was 100% compared 37.9% 55.2% those RHT, respectively. of death group increased delayed thrombolysis (p = 0.009, odds ratio (OR) 1.73 95% CI (confidence interval) 1.14–2.62), D-dimer concentration 0.02, OR 1.43 1.06–1.93), decreased PaO2/FiO2 0.001, 0.56 0.41–0.78). receiver operating characteristic method determined that a 1-day delay thrombolytic treatment, >5.844 mg/L, <144 mmHg predicted fatal outcome. severe ARDS increases higher levels, PaO2/FiO2, treatment. Thrombolysis seems be treatment choice RHT. It should carried out as soon possible after diagnosis established.

Language: Английский

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Mortality, Intensive Care Unit Admission, and Intubation among Hospitalized Patients with COVID-19: A One-Year Retrospective Study in Jordan

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(7), P. 2651 - 2651

Published: April 2, 2023

COVID-19 is a public health crisis that has caused numerous deaths, necessitated an increased number of hospital admissions, and led to extended inpatient stays. This study aimed identify the factors associated with mortality, intensive care unit admission, intubation, length stay among Jordanian patients. was one-year retrospective 745 patients admitted Jordan University Hospital. Data regarding patients' demographics, clinical co-morbid conditions, imaging, laboratory parameters, admission (ICU), intubation were collected from their medical records using coding manual. The data revealed overall rates COVID-19-related ICU invasive 23.0%, 28.3%, 10.8%, respectively. Chronic kidney disease (CKD), troponin, lactate dehydrogenase (LDH), O2 saturation <90% significantly mortality rate. variables heart failure use remdesivir. However, gastrointestinal (GI) symptoms only intubation. findings this suggest study-related outcomes can be used predict severity COVID-19, they inform future research aiming specific populations who are at higher risk complications.

Language: Английский

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COVID-19, Possible Hepatic Pathways and Alcohol Abuse—What Do We Know up to 2023?

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2212 - 2212

Published: Feb. 12, 2024

The pandemic period due to coronavirus disease 2019 (COVID-19) revolutionized all possible areas of global health. Significant consequences were also related diverse extrapulmonary manifestations this pathology. liver was found be a relatively common organ, beyond the respiratory tract, affected by severe acute syndrome coronavirus-2 (SARS-CoV-2). Multiple studies revealed essential role chronic (CLD) in general outcome infection. Present concerns field are direct hepatic caused COVID-19 and pre-existing disorders as risk factors for course Which mechanism has key phenomenon—previously existing disorder or failure SARS-CoV-2—is still not fully clarified. Alcoholic (ALD) constitutes another elucidated context Should toxic effects ethanol already developed cirrhosis its perceived causative triggering factor impairment patients? In face these discrepancies, we decided summarize whole picture infection, paying special attention ALD focusing on pathological pathways COVID-19, toxicity cirrhosis.

Language: Английский

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Favipiravir, remdesivir, and lopinavir: metabolites, degradation products and their analytical methods

Drug Metabolism Reviews, Journal Year: 2024, Volume and Issue: 56(2), P. 127 - 144

Published: March 6, 2024

Severe acute respiratory syndrome 2 (SARS-CoV-2) caused the emergence of COVID-19 pandemic all over world. Several studies have suggested that antiviral drugs such as favipiravir (FAV), remdesivir (RDV), and lopinavir (LPV) may potentially prevent spread virus in host cells person-to-person transmission. Simultaneously with widespread use these drugs, their stability action mechanism also attracted attention many researchers. This review focuses on mechanism, metabolites degradation products (FAV, RDV LPV) demonstrates various methods for quantification discrimination different biological samples. Herein, instrumental analysis main form or metabolite are classified into two types: optical chromatography which last one combination detectors provides a powerful method routine analyses. Some representative reported this details them carefully explained. It is hoped will be good guideline study provide better understanding from aspects investigated study.

Language: Английский

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Molecular docking analysis of peptide-based antiviral agents against SARS-CoV-2 main protease: an approach towards drug repurposing

Exploration of Medicine, Journal Year: 2023, Volume and Issue: unknown, P. 33 - 44

Published: Feb. 27, 2023

Aim: Utilizing the therapeutic potentials of previously approved medications against a new target or pharmacological response is known as drug repurposing. The health and scientific communities are under continual pressure to discover compounds with antiviral potential due rising reports viral resistance occurrence re-emergence outbreaks. use peptides has emerged an intriguing option in this search. Here, article includes current United States Food Drug Administration (FDA)-approved that might be enforced for treatment severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection carried out docking study protease inhibitors. Methods: In silico techniques like molecular was using Autodock Vina software. Results: studies peptide-based agents SARS-CoV-2 [Protein Data Bank (PDB) ID: 7P35] software AutoDockTools 1.5.6. Among all docked ligands, compound velpatasvir showed interaction residues ILE213, GLN256, LEU141, GLN189, GLU166, HIS41, CYS145, ASN142, displayed highest score –8.2 kcal/mol. This medication could novel lead candidate treating SARS-CoV-2. Conclusions: To conclude, peptide based their binding mode catalytic domain receptor reported. On docking, have remarkable affinity amino acids chain A. occupied same cavity reference maintaining interactions conserved acid essential significant inhibitory potential, especially

Language: Английский

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Prophylactic and Therapeutic Potential Zinc Metallodrugs Drug Discovery: Identification of SARS-CoV-2 Replication and Spike/ACE2 Inhibitors

Current Computer - Aided Drug Design, Journal Year: 2022, Volume and Issue: 18(7), P. 519 - 534

Published: Sept. 23, 2022

Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) variants with novel spike protein mutations has been shown to be influencing the epidemiological and clinical aspects COVID-19 pandemic. Objective: Due studies showing various dietary benefits zinc as a viral replication inhibitor well an immunity enhancer, organometallic complexes incorporating ions can ideal antiviral candidates due their structural variation diverse stereochemistry. Methods: In silico were conducted for virtual screening SARSCoV- host proteins explore effect on entry activity. Molegro Virtual Docker along AutoDock was used identification potential SARS-CoV-2 from Cambridge Structural Database (CSD). Molecular dynamics (MD), density functional theory (DFT), chemical absorption, distribution, metabolism, excretion, toxicity properties (ADMET) support findings screening. Results: correlation RNA-dependent RNA polymerase receptorbinding domain bound ACE2 docking results, compound (bis(3,5-dimethyl-1H-pyrazole)- bis(2-furoato)-zinc(ii)) (CSD code ECOZAA) occurs metal complex receptor inhibitor. ECOZAA observed (in binding affinity = - 179.29kcal/mol) behave better than clinically approved drug Remdesivir -62.69kcal/mol) against polymerase. large HOMO- LUMO gap is indication low reactivity great kinetic stability compound. Conclusion: Thus, this study highlights use inhibitors.

Language: Английский

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