Antiviral Research, Journal Year: 2023, Volume and Issue: 217, P. 105681 - 105681
Published: July 25, 2023
Language: Английский
Frontiers in Plant Science, Journal Year: 2023, Volume and Issue: 14
Published: Feb. 24, 2023
Acidification can seriously affect the growth of tea trees and yield quality leaves. In this study, we analyzed effects acidification on physicochemical properties, microorganisms metabolites rhizosphere soils with different pH values, results showed that increase soil pH, organic matter content, cation exchange capacity, microbial biomass carbon, nitrogen, respiration intensity, bacterial number actinomyces in all an increasing trend, while fungi decreased. The metabolite analysis 2376, 2377 2359 were detected values 3.29, 4.74 5.32, respectively, similar compounds reached 2331, accounting for more than 98%. content total contents increased significantly. correlation between indexes significantly correlated 221 metabolites, among which 55 positively 166 negatively correlated. Based interaction network analysis, 59 characteristic obtained divided into 22 categories, 7 categories a significant trend other 15 opposite trend. functional study found rhizosphere, diversity increased, cyclic ability C N was enhanced, turn might lead to enhancement resistance tree promote tree.
Language: Английский
Citations
23
Viruses, Journal Year: 2025, Volume and Issue: 17(2), P. 138 - 138
Published: Jan. 21, 2025
The global spread of viral diseases is a public health issue. Ribavirin (RBV) and mycophenolic acid (MPA) are well-known wide-spectrum antiviral agents. present study evaluated the potential bovine serum albumin (BSA) nanoparticles (NPs) as vehicle to improve efficacy molecules with activity. results demonstrated that NPs offer promising strategy for delivery drugs, improving their stability reducing toxicity compared free BSA-based effectively encapsulated hydrophilic such MPA water-soluble compounds RBV, achieving encapsulation efficiencies 10% 20%, respectively. purified exhibited particle size between 60 100 nm did not show at concentrations. In cellular infection models against Zika virus (ZIKV), Junín (JUNV), vesicular stomatitis (VSV) herpes simplex (HSV-1), loaded or RBV properties superior those non-encapsulated agents, well 100- 200-fold effective dose reductions, These findings clearly indicate BSA novel platform development safer more efficient therapies.
Language: Английский
Citations
1
Antiviral Research, Journal Year: 2025, Volume and Issue: 236, P. 106099 - 106099
Published: Feb. 10, 2025
The emergence of new human viruses with epidemic or pandemic potential has reaffirmed the urgency to develop effective broad-spectrum antivirals (BSAs) as part a strategic framework for prevention and preparedness. To this end, host nucleotide metabolic pathway been subject intense investigation in search host-targeting agents (HTAs) BSA activity. In particular, dihydroorotate dehydrogenase (hDHODH), rate-limiting enzyme de novo pyrimidine biosynthetic pathway, identified preferential target HTAs. Viral replication fact relies on cellular replenishment, making hDHODH an ideal HTA target. depletion pool that ensues pharmacological inhibition activity elicits through three distinct mechanisms: it blocks viral DNA RNA synthesis; activates effector mechanisms innate antiviral response; mitigates virus-induced inflammatory response. However, despite spectacular results obtained vitro, inhibitors examined mono-drug therapies animal models infections clinical trials have produced disappointing levels overall efficacy. overcome inherent limitation, strategies based multi-drug combination treatments should be considered enable efficacy hDHODH-targeted therapies. Here, we review state-of-the-art applications inhibitors, discuss challenges emerged from their testing consider how they might addressed advance development treatment diseases.
Language: Английский
Citations
1
Redox Biology, Journal Year: 2024, Volume and Issue: 71, P. 103112 - 103112
Published: March 4, 2024
The Warburg effect, also referred as aerobic glycolysis, is a common metabolic program during viral infection. Through targeted metabolomics combined with biochemical experiments and various cell models, we investigated the central carbon metabolism (CCM) profiles of cells infected porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus zoonotic potential. We found that PDCoV infection required glycolysis but decreased glycolytic flux, exhibiting non-Warburg effect characterized by pyruvic acid accumulation. Mechanistically, enhanced pyruvate kinase activity to promote anabolism, process generates concomitant ATP production. hijacked catabolism increase biosynthesis non-essential amino acids (NEAAs), suggesting essential hub for scavenge host energy metabolites. Furthermore, facilitated glutaminolysis synthesis NEAA pyrimidines optimal proliferation. Our work supports novel CCM model after provides potential anti-PDCoV drug targets.
Language: Английский
Citations
4
PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(5), P. e1013164 - e1013164
Published: May 19, 2025
Viruses modulate various aspects of host physiology, including carbon metabolism, redox balance, and mitochondrial bioenergetics to acquire the building blocks for replication regulation immune response. Understanding how SARS-CoV-2 alters metabolism may lead treatments COVID-19. We report that a ubiquitous gaseous molecule, hydrogen sulfide (H 2 S), regulates redox, control SARS-CoV-2. Virus is associated with down-regulation H S-producing enzymes cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CTH), 3-mercaptopyruvate sulfurtransferase (3-MST) in multiple cell lines nasopharyngeal swabs symptomatic COVID-19 patients. Consequently, SARS-CoV-2-infected cells showed diminished endogenous S levels protein modification (S-sulfhydration) caused by S. Genetic silencing or chemical inhibition CTH resulted proliferation. Chemical supplementation using slow-releasing donor, GYY4137, virus replication. Using biosensor, metabolomics, transcriptomics, XF-flux analyzer, we GYY4137 blocked inducing Nrf2/Keap1 pathway, restoring balance metabolites potentiating oxidative phosphorylation. Treatment mice hamsters suppressed viral ameliorated lung pathology. treatment reduced expression inflammatory cytokines re-established Nrf2-dependent antioxidant genes lungs mice. Notably, non-invasive measurement respiratory functions unrestrained whole-body plethysmography (uWBP) improved pulmonary function variables, obstruction (Penh), end-expiratory pause (EEP), relaxation time (RT) upon treatment. Together, our findings significantly extend understanding S-mediated infections open new avenues investigating pathogenic mechanisms therapeutic opportunities coronavirus-associated disorders.
Language: Английский
Citations
0
Viruses, Journal Year: 2023, Volume and Issue: 16(1), P. 35 - 35
Published: Dec. 24, 2023
Metabolic enzymes are central players for cell metabolism and proliferation. These perform distinct functions in various cellular processes, such as immune defense. Because viral infections inevitably trigger host activation, viruses have evolved diverse strategies to blunt or exploit the response enable replication. Meanwhile, hijack key metabolic reprogram metabolism, which generates necessary biomolecules An emerging theme arising from studies of infection is that and, conversely, components regulate revealing unexpected communication between these two fundamental processes otherwise disjointed. This review aims summarize our present comprehension involvement immunity provide insights potential antiviral therapy targeting enzymes.
Language: Английский
Citations
6
Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(2), P. 174 - 174
Published: Jan. 30, 2024
The use of azathioprine (AZA) in human medicine dates back to research conducted 1975 that led the development several drugs, including 6-mercaptopurine. In 1958, it was shown 6-mercaptopurine decreased production antibodies against earlier administered antigens, raising hypothesis an immunomodulatory effect. AZA is a prodrug belongs thiopurine group drugs behave as purine analogs. After absorption, converted into Subsequently, can be degraded through various enzymatic pathways inactive compounds and biologically active related mechanism action, which has been subject study evaluate possible antiviral This aims examine metabolism, potential its derivatives, exploring impact on targets adverse effects narrative literature review. Ultimately, review will provide insights mechanism, present evidence vitro effectiveness DNA RNA viruses, suggest vivo studies further demonstrate effects.
Language: Английский
Citations
2
International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 265, P. 131023 - 131023
Published: March 19, 2024
Language: Английский
Citations
2
Antiviral Research, Journal Year: 2023, Volume and Issue: 219, P. 105734 - 105734
Published: Oct. 16, 2023
Human respiratory syncytial virus (RSV) is an important cause of acute lower infections, for which no effective drugs are currently available. The development new anti-RSV agents therefore urgent priority, and Host-Targeting Antivirals (HTAs) can be considered to target RSV infections. As a contribution this antiviral avenue, we have characterized the molecular mechanisms activity MEDS433, inhibitor human dihydroorotate dehydrogenase (hDHODH), key cellular enzyme de novo pyrimidine biosynthesis. MEDS433 was found exert potent against RSV-A RSV-B in one-digit nanomolar range. Analysis replication cycle MEDS433-treated cells, revealed that hDHODH suppressed synthesis viral genome, consistently with its ability specifically enzymatic activity. Then, capability induce expression proteins encoded by Interferon-Stimulated Genes (ISGs) identified as second mechanism RSV. Indeed, stimulated secretion IFN-β IFN-λ1 that, turn, induced some ISG proteins, such IFI6, IFITM1 IRF7. Singly these reduced replication, thus likely contributing overall MEDS433. Lastly, proved even primary small airway epithelial cell model. Taken whole, observations provide insights further promising candidate develop strategies treatment
Language: Английский
Citations
5
ChemistrySelect, Journal Year: 2023, Volume and Issue: 8(48)
Published: Dec. 21, 2023
Abstract The study focused on developing new triazolopyrimidine derivatives as potential DNA Gyrase inhibitors and antimicrobial agents. compounds were designed, synthesized, evaluated for their biological activities, safety, ADMET properties. Encouragingly, the initial results showed promising potency acceptable ADME parameters, forming a strong basis further drug development research. newly synthesized verified through spectra, mass, elemental analysis. Notably, several exhibited significant activity against both Gram‐positive Gram‐negative bacteria, with MIC values ranging from 100 μg/ml to 250 μg/ml. importantly, found be safe, no reported adverse effects or toxicities. Among tested compounds, compound 2 m stood out an excellent inhibitor, IC50 value of 0.89 μM, comparable reference ciprofloxacin 0.91 μM. Molecular docking studies confirmed that compounds′ binding mode scores similar ciprofloxacin, validating antibacterial via inhibition. research provides valuable insights into these Their safe profile make them candidates
Language: Английский
Citations
2