Preučevanje mehanizma inhibicije rožmarinske kisline na glavni proteazi sars-cov-2 z dinamičnimi simulacijami : magistrsko delo

Žižek, Amanda

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Title:	Preučevanje mehanizma inhibicije rožmarinske kisline na glavni proteazi sars-cov-2 z dinamičnimi simulacijami : magistrsko delo
Authors:	ID Žižek, Amanda (Author) ID Bren, Urban (Mentor) More about this mentor... ID Lešnik, Samo (Comentor)
Files:	MAG_Zizek_Amanda_2026.pdf (2,13 MB) MD5: 5741C3CCE72AA25A8C3CB46E954E12B9
Language:	Slovenian
Work type:	Master's thesis/paper
Typology:	2.09 - Master's Thesis
Organization:	FKKT - Faculty of Chemistry and Chemical Engineering
Abstract:	SARS-CoV-2 je virus z visoko stopnjo mutacij in izrazito nalezljivostjo, kar predstavlja velik izziv za razvoj učinkovitih protivirusnih terapij. Ena ključnih tarč za zdravljenje bolezni COVID-19 je glavna proteaza (Mpro), ki ima bistveno vlogo pri proteolitski cepitvi virusnih poliproteinov in s tem omogoča replikacijo virusa. Zaviranje delovanja tega encima predstavlja obetaven pristop k preprečevanju razmnoževanja virusa. Naravni produkti, zlasti polifenolne spojine, so zaradi nizke toksičnosti in raznolikega biološkega delovanja zanimiv vir novih protivirusnih učinkovin. Ena izmed takšnih spojin je rožmarinska kislina, naravna fenolna kislina, prisotna v rastlinah družin Boraginaceae in Lamiaceae, ki izkazuje antioksidativno, protivnetno in protivirusno delovanje. Cilj magistrskega dela je bil preučiti mehanizem inhibicije rožmarinske kisline na glavni proteazi SARS-CoV-2 z uporabo simulacij molekulske dinamike. V okviru dela je bila uporabljena kristalna struktura kompleksa Mpro z rožmarinsko kislino iz baze Protein Data Bank (8YRH). Priprava simulacijskega sistema je potekala v programu CHARMM-GUI, molekulska dinamika je bila izvedena s programom NAMD, analiza rezultatov pa z orodjema Chimera in Cytoscape. Simulacija v dolžini 100 ns je omogočila vpogled v stabilnost kompleksa ter dinamiko vezave liganda v aktivnem mestu encima. Analiza parametrov stabilnosti je pokazala, da prisotnost rožmarinske kisline poveča strukturno stabilnost proteaze, analiza vodikovih vezi pa je razkrila pomembne interakcije z aminokislinskimi ostanki aktivnega mesta. Pridobljeni rezultati potrjujejo potencial rožmarinske kisline kot naravnega inhibitorja Mpro in predstavljajo osnovo za nadaljnje racionalno načrtovanje izboljšanih protivirusnih učinkovin.
Keywords:	SARS-CoV-2, Mpro, rožmarinska kislina, molekulska dinamika, računalniške simulacije
Place of publishing:	Maribor
Place of performance:	Maribor
Publisher:	[A. Žižek]
Year of publishing:	2026
Number of pages:	1 spletni vir (1 datoteka PDF (VIII, 29 str.))
PID:	20.500.12556/DKUM-97722
UDC:	615.281.8:582.943.16(043.2)
COBISS.SI-ID:	277132291
Publication date in DKUM:	04.05.2026
Views:	181
Downloads:	33
Metadata:
Categories:	KTFMB - FKKT
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Licences

License:	CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International

Link:	http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:	The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Licensing start date:	07.04.2026

Secondary language

Language:	English
Title:	Studying the inhibition mechanism of rosmarinic acid on sars-cov-2 major protease by dynamic simulations
Abstract:	SARS-CoV-2 is characterized by a high mutation rate and strong infectivity, which represents a major challenge for the development of effective antiviral therapies. One of the most important therapeutic targets for the treatment of COVID-19 is the SARS-CoV-2 main protease (Mpro), which plays a crucial role in the proteolytic cleavage of viral polyproteins and is therefore essential for viral replication. Inhibition of this enzyme represents a promising strategy for suppressing viral proliferation. Natural products, particularly polyphenolic compounds, are of increasing interest as potential antiviral agents due to their low toxicity and diverse biological activities. One such compound is rosmarinic acid, a natural phenolic acid found in plants of the Boraginaceae and Lamiaceae families, which exhibits antioxidant, anti-inflammatory, and antiviral properties. The aim of this master’s thesis was to investigate the inhibition mechanism of rosmarinic acid on the SARS-CoV-2 main protease using molecular dynamics simulations. The crystal structure of the Mpro–rosmarinic acid complex (8YRH) was used as the starting model. System preparation was performed using CHARMM-GUI, molecular dynamics simulations were carried out with NAMD, and trajectory analysis was conducted using Chimera and Cytoscape. A 100 ns molecular dynamics simulation provided insights into the stability of the protein–ligand complex and the dynamic behavior of rosmarinic acid within the active site of Mpro. Analyses of stability parameters demonstrated that the presence of rosmarinic acid increases the structural stability of the protease. Hydrogen bond analysis revealed key interactions between rosmarinic acid and important active-site residues. The obtained results confirm the inhibitory potential of rosmarinic acid and provide a valuable basis for the rational design of improved natural inhibitors targeting the SARS-CoV-2 main protease.
Keywords:	SARS-CoV-2, Mpro, rosmarinic acid, molecular dynamics, computer simulations

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