Iskanje po repozitoriju

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Povzetek: Coronavirus disease-2019 (COVID-19) has become a global pandemic, necessitating the development of new medicines. In this investigation, we identified potential natural flavonoids and compared their inhibitory activity against spike glycoprotein, which is a target of SARS-CoV-2 and SARS-CoV. The target site for the interaction of new inhibitors for the treatment of SARS-CoV-2 has 82% sequence identity and the remaining 18% dissimilarities in RBD S1-subunit, S2-subunit, and 2.5% others. Molecular docking was employed to analyse the various binding processes used by each ligand in a library of 85 natural flavonoids that act as anti-viral medications and FDA authorised treatments for COVID-19. In the binding pocket of the target active site, remdesivir has less binding interaction than pectolinarin, according to the docking analysis. Pectolinarin is a natural flavonoid isolated from Cirsiumsetidensas that has anti-cancer, vasorelaxant, anti-inflammatory, hepatoprotective, anti-diabetic, anti-microbial, and anti-oxidant properties. The S-glycoprotein RBD region (330–583) is inhibited by kaempferol, rhoifolin, and herbacetin, but the S2 subunit (686–1270) is inhibited by pectolinarin, morin, and remdesivir. MD simulation analysis of S-glycoprotein of SARS-CoV-2 with pectolinarin complex at 100ns based on high dock-score. Finally, ADMET analysis was used to validate the proposed compounds with the highest binding energy.
Ključne besede: coronaviruses, SARS-CoV-2, S-glycoproteins, computational analysis
Objavljeno v DiRROS: 16.12.2025; Ogledov: 226; Prenosov: 91
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Povzetek: Introduction: The classification of antiphospholipid syndrome (APS) comprises clinical criteria (vascular thrombosis or obstetric complications throughout life) and laboratory criteria (antiphospholipid antibodies (aPLs) positivity, confirmed at least twice at 12-week interval). Methods: In 100 patients admitted to the hospital with COVID-19 pneumonia, thrombosis and pregnancy complications were recorded during the hospital stay and in personal medical history. They were tested for nine types of aPLs at four time points (admission, deterioration, discharge, and 3-month follow-up): anticardiolipin (aCL), anti-β2-glycoproteinI (anti-β2GPI), and antiphosphatidylserine/prothrombin (aPS/PT) isotypes IgM/IgG/IgA. Results: During hospitalization, aPLs were detected at least once in 51% of patients. All 7% of deceased patients tested negative for aPLs upon admission, and only one patient became aCL IgG positive as his condition worsened. In 83.3% of patients, intrahospital thrombosis was not related to aPLs. One patient with pulmonary artery and cerebral artery thrombosis was given an APS diagnosis (triple aPLs positivity on admission, double on follow-up). Personal anamnesis (PA) for thromboembolism was verified in 10 patients, all of whom tested negative for aPLs at admission; however, transition to aPLs positivity at discharge (as the disease subsided) was seen in 60% of patients: three of six with arterial thrombosis (at follow-up, two did not appear, and one was negativized) and three of four with deep vein thrombosis (one was confirmed at follow-up and diagnosed with APS, one was negativized, and one did not appear). At admission, the majority of the aPLs were of the aCL IgG class (58.8%). Unexpectedly, as the COVID-19 disease decreased, anti-β2GPI IgG antibodies (linked with thromboses) became newly positive at discharge (14.9%), as confirmed at follow-up (20.8%). Conclusion: The incidence of APS in our cohort was 2.0%, whereas in the general population, it ranges from 0.001% to 0.002%. The incidence might have increased even more if the four aPLs-positive patients with intrahospital thrombosis/history of thrombosis had attended follow-up. Recommendation: All patients with severe COVID-19 or post-COVID syndrome should be evaluated for current/previous thrombosis and tested for aPLs at least twice: at admission to the hospital and at discharge, then retested 3 months later in positive cases in order to be given the appropriate therapy.
Ključne besede: COVID-19, SARS-CoV2, anti-phosphatidylserine-prothrombin (aPS/PT) antibodies, anti-β2-glycoprotein I (anti-β2GPI) antibodies, anticardiolipin (aCL) antibodies, antiphospholipid antibodies (aPLs), antiphospholipid syndrome, immunology, post-COVID syndrome, vascular thrombosis
Objavljeno v DiRROS: 01.12.2025; Ogledov: 210; Prenosov: 97
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Povzetek: The SARS-CoV-2 envelope protein (2-EPRO), a viroporin crucial for viral pathogenesis, is a promising target for antiviral drug development as it is highly conserved and functionally important. Although it is a promising therapeutic target for the treatment of COVID-19, it has often been overlooked in previous studies. In this study, a high-throughput virtual screening of nearly one billion compounds was performed, followed by rigorous filtering and re-docking. Eight best-scoring and chemically versatile lead candidates were identified. In molecular dynamics simulations, three of these ligands showed stable protein-ligand complexes occupying the 2-EPRO channel pore. Among these, ZINC001799167680 (L3) and ZINC001081252239 (L2) exhibited the strongest binding a˙inity, with key interactions at residues ASN15, THR11 and GLU8 identified by Molecular Mechanics Poisson-Boltzmann Surface Area analysis. All ligands were compared with the known inhibitor rimantadine and showed stronger binding to the protein. These in silico results highlight the potential of focusing on the 2-EPRO ion channel in the development of novel COVID-19 therapeutics and pave the way for further in vitro and in vivo studies.
Ključne besede: SARS-CoV-2 envelope protein, viroporin, ion channel, channel blockers, molecular dynamics simulations, free energy calculations, drug discovery
Objavljeno v DiRROS: 05.09.2025; Ogledov: 406; Prenosov: 158
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Povzetek: In the beginning of 2020, the outbreak of the COVID-19 pandemic led to a crisis in which diagnostic methods for the genome detection of SARS-CoV-2 were urgently needed. Based on the very early publication of the basic principles for a diagnostic test for the genome detection of SARS-CoV-2, the first noncommercial laboratory-developed tests (LDTs) and commercial tests were introduced. As there was considerable uncertainty about the reliability and performance of different tests and different laboratories, INSTAND established external quality assessment (EQA) schemes for the detection of SARS-CoV-2 starting in April 2020. In close partnership in a scientific network, the EQA schemes were enhanced, especially the April, June and November 2020 terms. The enhancement included: (i) immediate provision of suitable virus including variants of concern at the beginning of the pandemic outbreak, (ii) short frequency of EQA schemes, (iii) concentration dependency of the testing and sensitivity check, achieved by using SARS-CoV-2-positive samples from a 10-fold dilution series of the same starting material, (iv) specificity check of the testing, achieved by using SARS-CoV-2-negative samples containing human coronaviruses or MERS CoV, (v) revealed samples for orientation on test performance during an ongoing or at the start of an EQA scheme using a pre-quantified SARS-CoV-2-positive EQA sample with a low viral RNA load of only 1 570 copies/mL assigned by digital PCR (dPCR) in June 2020 and (vi) quantified reference materials based on the experiences of the first two EQA schemes with dPCR-assigned values in copies/mL beginning in November 2020 for self-evaluation of the applied test system. This manuscript summarizes the results of a total of 13 EQA schemes for the detection of SARS-CoV-2 between April 2020 and June 2023 in which a total of 1 413 laboratories from 49 countries participated. The qualitative results for the detection of SARS-CoV-2-positive samples were between 95.8 % and 99.7 % correct positive, excluding extremely low concentration samples. For all SARS-CoV-2-negative EQA samples, the qualitative success rates ranged from 95.1 % to 99.4 % correct negative results. The widely varying values for the cycle threshold (Ct)/crossing point (Cq) reported for the different target genes and test systems were striking. A few laboratories reported quantitative results in copies/mL for several VOCs with an acceptable rate of over 93 % correct positive results in the majority of cases. The description of the enhanced EQA schemes for SARS-CoV-2 detection in terms of timing and scope can serve as a blueprint for the rapid development of a quality assessment of diagnostics for an emerging pathogen.
Ključne besede: COVID-19 pandemic, SARS-CoV-2, virus genome detection tests, reference materials, external quality assessment, laboratory medicine, epidemiology
Objavljeno v DiRROS: 18.06.2025; Ogledov: 592; Prenosov: 490
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Povzetek: With their unique physicochemical properties, such as metallic-like conductivity, favorable (electro)catalytic properties, electrochemical stability, and ease of functionalization, pyrochlores have found applications in various fields such as solid oxide fuel cells, batteries, thick film resistors, and temperature sensors; however, there are no reports on their application in electrochemical immunosensing. In this study, we exploited the (electro)catalytic nature and stability of the pyrochlore Bi2Ru2O7 clusters silanized with (3-aminopropyl)triethoxysilane (APTES) to demonstrate their potential for the effective stacking of functional proteins. Characterization of the clusters by XPS disclosed a dual environment of Bi, also indicating the presence of Bi2O3 alongside APTES-Bi2Ru2O7 clusters and, importantly, the predominant involvement of pyrochlore moieties in subsequent protein stacking. After stacking protein A and antibodies, the immunosensor revealed a nearly interference-free operation, high sensitivity, a detection limit of 118 fM SARS-CoV-2 spike protein, and operation in a wide examined concentration range of 10−5−10−1 μg mL−1 with an r2 of 0.98. In combination with a short incubation time of 30 min, the pyrochlore-based immunosensor provides a solid platform for future point-of-need applications.
Ključne besede: Bi2Ru2O7 pyrochlore, APTES, SARS-CoV-2, spike protein, immunosensors, electrochemical
Objavljeno v DiRROS: 24.03.2025; Ogledov: 745; Prenosov: 437
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