Evaluation of the inhibitory effect of compounds from halophyte Salicornia sp. extract against the SARS-CoV-2 main protease via molecular docking simulations and an in vitro assay

Σαπουντζάκη, Ελευθερία; Sapountzaki, Eleftheria

dc.contributor.author	Σαπουντζάκη, Ελευθερία	el
dc.contributor.author	Sapountzaki, Eleftheria	en
dc.date.accessioned	2022-07-25T10:23:11Z
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/55491
dc.identifier.uri	http://dx.doi.org/10.26240/heal.ntua.23189
dc.rights	Default License
dc.subject	Ενζυμική παρεμπόδιση	el
dc.subject	Προσομοίωση μοριακής πρόσδεσης	el
dc.subject	Αντιική δράση	el
dc.subject	Enzyme inhibition	en
dc.subject	Molecular docking	en
dc.subject	Salicornia	en
dc.subject	SARS-CoV-2	en
dc.subject	Antiviral	en
dc.subject	SARS-CoV-2	en
dc.subject	Salicornia	en
dc.title	Evaluation of the inhibitory effect of compounds from halophyte Salicornia sp. extract against the SARS-CoV-2 main protease via molecular docking simulations and an in vitro assay	en
heal.type	bachelorThesis
heal.secondaryTitle	Διερεύνηση της ανασταλτικής δράσης συστατικών του εκχυλίσματος από το αλόφυτο Salicornia sp. ενάντια στη κύρια πρωτεάση του ιού SARS-CoV-2 μέσω μοριακής πρόσδεσης και in vitro δοκιμής	el
heal.classification	Biotechnology	en
heal.dateAvailable	2023-07-24T21:00:00Z
heal.language	en
heal.access	embargo
heal.recordProvider	ntua	el
heal.publicationDate	2021-10-04
heal.abstract	The world is currently going through the second year of a pandemic, which started on March, 2020, and has had numerous cases and victims and enormous consequences on social and economic life. The cause of this pandemic is the newly identified SARS-CoV-2, an RNA virus of the family of Coronoviridae. Although various vaccines have been developed and vaccinations are ongoing, the antiviral drugs employed are limited and mostly already known repurposed drugs, so there is a need for additional ways to boost our defense against the virus. Phytochemicals emerge as a possible immune boosting solution that can act synergistically with pharmaceutical products, since many of them have proved to be active against various viruses. Particularly the extract of halophyte Salicornia contains a broad variety of compounds (hydroxycinnamic acids, hydroxybenzoic acids, caffeoyl quinic acids and their derivatives, flavonoids and flavanones, sterols, chromones, lignans, oleanane triterpenoid saponins), including molecules with confirmed antiviral properties, among numerous health benefits. Aim of this thesis is to initially utilize in silico methods (molecular docking using the YASARA Structure software), to perform a screening of the contents of the Salicornia extract for their inhibitory potential against the main protease of SARS-CoV-2 (Mpro), whose vital role in viral replication makes it an ideal target for the development of antiviral agents. As second step, the most promising compounds were tested in vitro, using an enzyme inhibition assay, together with an extract from a Salicornia plant. Docking and visualizing already confirmed and co-crystallized Mpro inhibitors was done in order to establish the method and obtain additional data on the binding mode mechanisms that result in effective inhibition. The simulation was then performed for the Salicornia constituents and resulted in an assessment of binding energies and contacting residues between the protease and each tested compounds. Caffeoylquinic acids and their z derivatives together with flavonoids and flavanones were highlighted as the most promising groups of compounds, with binding energies ranging from -7.9 to -8.935 kcal/ mol for the first group (excluding quinic acid) and -6.88 to -9.384 kcal/mol for the second group. The latter binding energy corresponds to the highest scoring compound, isorhamnetin-3-O-rutinoside. Patterns connecting the structure of the compounds and their binding affinity to the active site of Mpro were also detectable, the major one being that glycosylated compounds have a higher binding affinity to the enzyme than their parent structures. In vitro screening involved a selection of compounds based on the results of the preceding step, their commercial availability and how well they represent the variety of compounds present in the extract. Results were very encouraging, with the majority of the compounds inhibiting the activity of Mpro and a correlation between the molecular docking results and the IC50 (the concentration of a compound that results in 50% inhibition of the enzyme) calculations being indicated. The compound with the lowest IC50 was rutin (IC50=286.93 μΜ), followed by kaempferol (IC50=341.85 μΜ) and isorhamnetin-3-rutinoside (IC50=351.81 μΜ). Very promising results were also yielded for the crude Salicornia extract, which showed inhibitory activity with an IC50 of 400.66 kcal/mol. The assay results mainly confirmed the molecular docking results, providing useful information on which further investigation, both in vitro in cells and in vivo, could rely on. From the present findings, it is suggested that Salicornia extract and its contents can be valuable nutraceuticals and potential contributors to the fight against the ongoing pandemic.	en
heal.sponsor	Η παρούσα διπλωματική εργασία έγινε στα πλαίσια του προγράμματος ανταλλαγής Erasmus+ στο Luleå University of Technology, Department of Biochemical Process Engineering	en
heal.advisorName	Αντωνοπούλου, Ιώ	el
heal.committeeMemberName	Τόπακας, Ευάγγελος	el
heal.committeeMemberName	Μαμμά, Διομή	el
heal.committeeMemberName	Σαρίμβεης, Χαράλαμπος	el
heal.academicPublisher	Εθνικό Μετσόβιο Πολυτεχνείο. Σχολή Χημικών Μηχανικών	el
heal.academicPublisherID	ntua
heal.fullTextAvailability	false