WoS İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6
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Article The Effect of Vitamin D and Paricalcitol on Protein Disulfide Isomerase(Marmara University, 2025) Koksal, Murat; Şekerler, Turgut; Şener, Azize; Koksal, Muhammed MuratProtein disulfide isomerase (PDI), a multifunctional protein plays an important role as oxidoreductase, isomerase and chaperone in the cell. Prior studies have identified PDI is highly expressed in many different cancer types and presented as a new potential target for cancer treatment. Here, we investigated vitamin D and its analogue paricalcitol in silico interaction of the human PDI and inhibition of PDI reductase activity in vitro. We observed a non-covalent mechanism where the main skeleton of the vitamin D3 ans paricalcitol sturcture is located at the hydrophobic site in the b' domain of PDI and forms a hydrogen bond with a residue (His138) in tihs domain. They also form multiple weak hydrophobic interactions with various chemical groups of the b' subunit. For the first time, we demonstrate that 1,25-dihydroxyvitamin D3 (1a,25(OH)2 vitamin D3) and paricalcitol inhibit the PDI reductase activity in vitro and their IC50 values are 20.79±1.43 nmol/L and 32.83±3.15 nmol/L respectively. The two compounds can also block the denistrosation activity of PDI.Article Citation - WoS: 1Citation - Scopus: 1In Silico Evaluation of H1-Antihistamine as Potential Inhibitors of SARS-CoV RNA-Dependent RNA Polymerase: Repurposing Study of COVID-19 Therapy(Turkish Pharmacists Association, 2024) Küçükgüzel, İlkay; Kulabaş, Necla; Hamdan, MazınIntroduction: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), from the family Coronaviridae, is the seventh known coronavirus to infect humans and cause acute respiratory syndrome. Although vaccination efforts have been conducted against this virus, which emerged in Wuhan, China, in December 2019 and has spread rapidly around the world, the lack of an Food and Drug Administration-approved antiviral agent has made drug repurposing an important approach for emergency response during the COVID-19 pandemic. The aim of this study was to investigate the potential of H1-antihistamines as antiviral agents against SARS-CoV-2 RNA-dependent RNA polymerase enzyme. Materials and Methods: Using molecular docking techniques, we explored the interactions between H1-antihistamines and RNA-dependent RNA polymerase (RdRp), a key enzyme involved in viral replication. The three-dimensional structure of 37 H1-antihistamine molecules was drawn and their energies were minimized using Spartan 0.4. Subsequently, we conducted a docking study with Autodock Vina to assess the binding affinity of these molecules to the target site. The docking scores and conformations were then visualized using Discovery Studio. Results: The results examined showed that the docking scores of the H1-antihistamines were between 5.0 and 8.3 kcal/mol. These findings suggested that among all the analyzed drugs, bilastine, fexofenadine, montelukast, zafirlukast, mizolastine, and rupatadine might bind with the best binding energy (< -7.0 kcal/mol) and inhibit RdRp, potentially halting the replication of the virus. Conclusion: This study highlights the potential of H1-antihistamines in combating COVID-19 and underscores the value of computational approaches in rapid drug discovery and repurposing efforts. Finally, experimental studies are required to measure the potency of H1-antihistamines before their clinical use against COVID-19 as RdRp inhibitors.