PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397
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Article Citation - WoS: 33Citation - Scopus: 37In Silico Evaluation of Food-Derived Carotenoids Against SARS-CoV Drug Targets: Crocin Is a Promising Dietary Supplement Candidate for COVID-19(Wiley, 2022-05-11) Mujwar, Somdutt; Sun, Lei; Fidan, OzkanThe current COVID-19 pandemic is severely threatening public healthcare systems around the globe. Some supporting therapies such as remdesivir, favipiravir, and ivermectin are still under the process of a clinical trial, it is thus urgent to find alternative treatment and prevention options for SARS-CoV-2. In this regard, although many natural products have been tested and/or suggested for the treatment and prophylaxis of COVID-19, carotenoids as an important class of natural products were underexplored. The dietary supplementation of some carotenoids was already suggested to be potentially effective in the treatment of COVID-19 due to their strong antioxidant properties. In this study, we performed an in silico screening of common food-derived carotenoids against druggable target proteins of SARS-CoV-2 including main protease, helicase, replication complex, spike protein and its mutants for the recent variants of concern, and ADP-ribose phosphatase. Molecular docking results revealed that some of the carotenoids had low binding energies toward multiple receptors. Particularly, crocin had the strongest binding affinity (-10.5 kcal/mol) toward the replication complex of SARS-CoV-2 and indeed possessed quite low binding energy scores for other targets as well. The stability of crocin in the corresponding receptors was confirmed by molecular dynamics simulations. Our study, therefore, suggests that carotenoids, especially crocin, can be considered an effective alternative therapeutics and a dietary supplement candidate for the prophylaxis and treatment of SARS-CoV-2. Practical applications In this study, food-derived carotenoids as dietary supplements have the potential to be used for the prophylaxis and/or treatment of SARS-CoV-2. Using in silico techniques, we aimed at discovering food-derived carotenoids with inhibitory effects against multiple druggable sites of SARS-CoV-2. Molecular docking experiments against main protease, helicase, replication complex, spike protein and its mutants for the recent variants of concern, and ADP-ribose phosphatase resulted in a few carotenoids with multitarget inhibitory effects. Particularly, crocin as one of the main components of saffron exhibited strong binding affinities to the multiple drug targets including main protease, helicase, replication complex, mutant spike protein of lineage B.1.351, and ADP-ribose phosphatase. The stability of the crocin complexed with these drug targets was further confirmed through molecular dynamics simulations. Overall, our study provides the preliminary data for the potential use of food-derived carotenoids, particularly crocin, as dietary supplements in the prevention and treatment of COVID-19.Article Citation - WoS: 31Citation - Scopus: 34Discovery of Adapalene and Dihydrotachysterol as Antiviral Agents for the Omicron Variant of SARS-CoV-2 Through Computational Drug Repurposing(Springer, 2022-05-04) Fidan, Ozkan; Mujwar, Somdutt; Kciuk, MateuszSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been significantly paralyzing the societies, economies and health care systems around the globe. The mutations on the genome of SARS-CoV-2 led to the emergence of new variants, some of which are classified as "variant of concern" due to their increased transmissibility and better viral fitness. The Omicron variant, as the latest variant of concern, dominated the current COVID-19 cases all around the world. Unlike the previous variants of concern, the Omicron variant has 15 mutations on the receptor-binding domain of spike protein and the changes in the key amino acid residues of S protein can enhance the binding ability of the virus to hACE2, resulting in a significant increase in the infectivity of the Omicron variant. Therefore, there is still an urgent need for treatment and prevention of variants of concern, particularly for the Omicron variant. In this study, an in silico drug repurposing was conducted through the molecular docking of 2890 FDA-approved drugs against the mutant S protein of SARS-CoV-2 for Omicron variant. We discovered promising drug candidates for the inhibition of alarming Omicron variant such as quinestrol, adapalene, tamibarotene, and dihydrotachysterol. The stability of ligands complexed with the mutant S protein was confirmed using MD simulations. The lead compounds were further evaluated for their potential use and side effects based on the current literature. Particularly, adapalene, dihydrotachysterol, levocabastine and bexarotene came into prominence due to their non-interference with the normal physiological processes. Therefore, this study suggests that these approved drugs can be considered as drug candidates for further in vitro and in vivo studies to develop new treatment options for the Omicron variant of SARS-CoV-2. [GRAPHICS] .Article Citation - WoS: 4Citation - Scopus: 5Can Mesenchymal Stem/Stromal Cells and Their Secretomes Combat Bacterial Persisters(Springer, 2023-08-12) Bicer, Mesude; Fidan, OzkanThe increasing number of life-threatening infections caused by persister bacteria is associated with various issues, including antimicrobial resistance and biofilm formation. Infections due to persister cells are often difficult to suppress without the use of last-resort antibiotics. Throughout the world, bacterial persistence and resistance create an unmet clinical demand for the exploration of newly introduced therapeutic approaches. Mesenchymal stem / stromal cells (MSCs) have an antimicrobial activity to protect against bacterial infections, including those caused by bacterial persisters. MSCs have substantial potential to secrete antimicrobial peptides (AMPs), including cathelicidin, beta-defensins, lipocalin-2, hepcidin, indoleamine 2,3-dioxygenase (IDO), cysteine proteases, and inducible nitric oxide synthases (iNOS). MSCs possess the potential to contribute to innate immunity by regulating the immune response. Recently, MSCs and their secreted components have been reported to improve antimicrobial activity. Bactericidal activity by MSCs and their secretomes has been shown to be mediated in part by the secretion of AMPs. Even though they were discovered more than 80 years ago, therapeutic options for persisters are restricted, and there is an urgent need for alternative treatment regimens. Hence, this review intends to critically assess the current literature on the effects of MSCs and their secretomes on persister bacteria. MSCs and their secretome-based therapies could be preferred as an up-and-coming approach to reinforce the antimicrobial efficiency in persister infections.