Design and various in silico studies of the novel curcumin derivatives as potential candidates against COVID-19-associated main enzymes

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dc.authoridDEMIR, KADIR/0000-0001-7312-3878
dc.authoridTAHTACI, HAKAN/0000-0002-1557-6315
dc.contributor.authorAlici, Hakan
dc.contributor.authorTahtaci, Hakan
dc.contributor.authorDemir, Kadir
dc.date.accessioned2024-09-29T15:55:10Z
dc.date.available2024-09-29T15:55:10Z
dc.date.issued2022
dc.departmentKarabük Üniversitesien_US
dc.description.abstractThe novel coronavirus disease (COVID-19) is a highly contagious disease caused by the SARS-CoV-2 virus, leading severe acute respiratory syndrome in patients. Although various antiviral drugs and their combinations have been tried so far against SARS-CoV-2 and they have shown some effectiveness, there is still a need for safe and cost-effective binding inhibitors in the fight against COVID-19. Therefore, phytochemicals in nature can be a quick solution due to their wide therapeutic spectrum and strong antiviral, anti-inflammatory, and antioxidant properties. In this context, the low toxicity, and high pharmacokinetic properties of curcumin, which is a natural phytochemical, as well as the easy synthesizing of its derivatives reveal the need for investigation of its various derivatives as inhibitors against coronaviruses. The present study focused on curcumin derivatives with reliable ADME profile and high molecular binding potency to different SARS-CoV-2 target enzymes (3CLPro, PLpro, NSP7/8/12, NSP7/8/12 +RNA, NSP15, NSP16, Spike, Spike+ACE). In the molecular docking studies, the best binding scores for the 22 proposed curcumin derivatives were obtained for the PLpro protein. Furthermore, MD simulations were performed for high-affinity ligand-PLpro protein complexes and subsequently, Lys157, Glu161, Asp164, Arg166, Glu167, Met208, Pro247, Pro248, Tyr264, Tyr273 and Asp302 residues of PLpro was deter-mined to play key role for ligand binding by Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) analysis. The results of the study promise that the proposed curcumin derivatives can be potent inhibitors against SARS-CoV-2 and be converted into pharmaceutical drugs. It is also expected that the findings may provide guiding insights to future design studies for synthesizing different antiviral derivatives of phytochemicals.en_US
dc.description.sponsorshipScientific Research Fund of Zonguldak Buelent Ecevit University [2015-22794455-03]en_US
dc.description.sponsorshipThis work was supported by the Scientific Research Fund of Zonguldak Buelent Ecevit University with project number 2015-22794455-03, and the numerical calculations reported in this paper were performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources) .en_US
dc.identifier.doi10.1016/j.compbiolchem.2022.107657
dc.identifier.issn1476-9271
dc.identifier.issn1476-928X
dc.identifier.pmid35259661en_US
dc.identifier.scopus2-s2.0-85125633911en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1016/j.compbiolchem.2022.107657
dc.identifier.urihttps://hdl.handle.net/20.500.14619/4505
dc.identifier.volume98en_US
dc.identifier.wosWOS:000793459900001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevier Sci Ltden_US
dc.relation.ispartofComputational Biology and Chemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectCoronavirusen_US
dc.subjectSARS-CoV-2en_US
dc.subjectMM-PBSAen_US
dc.subjectCurcuminen_US
dc.subjectDockingen_US
dc.subjectDrug designen_US
dc.subjectMolecular dynamicen_US
dc.subjectSimulationen_US
dc.titleDesign and various in silico studies of the novel curcumin derivatives as potential candidates against COVID-19-associated main enzymesen_US
dc.typeArticleen_US

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