1. Novel small-molecule inhibitors of the SARS-CoV-2 spike protein binding to neuropilin 1Anja Kolarič, Marko Jukič, Urban Bren, 2022, izvirni znanstveni članek Opis: Furin cleavage of the SARS-CoV-2 spike protein results in a polybasic terminal sequence
termed the C-end rule (CendR), which is responsible for the binding to neuropilin 1 (NRP1), enhancing
viral infectivity and entry into the cell. Here we report the identification of 20 small-molecule
inhibitors that emerged from a virtual screening of nearly 950,000 drug-like compounds that bind
with high probability to the CendR-binding pocket of NRP1. In a spike NRP1 binding assay, two of
these compounds displayed a stronger inhibition of spike protein binding to NRP1 than the known
NRP1 antagonist EG00229, for which the inhibition of the CendR peptide binding to NRP1 was
also experimentally confirmed. These compounds present a good starting point for the design of
small-molecule antagonists against the SARS-CoV-2 viral entry.
Ključne besede: neuropilin 1, SARS-CoV-2, COVID-19, spike binding inhibitors, virtual screening, small-molecule antagonists, molecular docking, in vitro binding assay
Objavljeno v DKUM: 09.05.2025; Ogledov: 0; Prenosov: 0
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2. Protein stacking on the APTES-functionalized pyrochlore ▫$Bi_2Ru_2O_7$▫ clusters for ultrasensitive and selective immunosensingNikola Tasić, Nika Vranešič, Dino Metarapi, Kristina Mervič, Milan Žunić, Aleksandra Dapčević, Matjaž Finšgar, Samo B. Hočevar, 2025, izvirni znanstveni članek Opis: With their unique physicochemical properties, such as metallic-like conductivity, favorable (electro)catalytic properties, electrochemical stability, and ease of functionalization, pyrochlores have found applications in various fields such as solid oxide fuel cells, batteries, thick film resistors, and temperature sensors; however, there are no reports on their application in electrochemical immunosensing. In this study, we exploited the (electro)catalytic nature and stability of the pyrochlore Bi2Ru2O7 clusters silanized with (3-aminopropyl)triethoxysilane (APTES) to demonstrate their potential for the effective stacking of functional proteins. Characterization of the clusters by XPS disclosed a dual environment of Bi, also indicating the presence of Bi2O3 alongside APTES-Bi2Ru2O7 clusters and, importantly, the predominant involvement of pyrochlore moieties in subsequent protein stacking. After stacking protein A and antibodies, the immunosensor revealed a nearly interference-free operation, high sensitivity, a detection limit of 118 fM SARS-CoV-2 spike protein, and operation in a wide examined concentration range of 10−5−10−1 μg mL−1 with an r2 of 0.98. In combination with a short incubation time of 30 min, the pyrochlore-based immunosensor provides a solid platform for future point-of-need applications.
Ključne besede: Bi2Ru2O7 pyrochlore, APTES, SARS-CoV-2, spike protein, immunosensors, electrochemical
Objavljeno v DKUM: 23.04.2025; Ogledov: 0; Prenosov: 1
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3. Recent developments in electrochemical-impedimetric biosensors for virus detectionZala Štukovnik, Urban Bren, 2022, pregledni znanstveni članek Opis: Viruses, including influenza viruses, MERS-CoV (Middle East respiratory syndrome coronavirus), SARS-CoV (severe acute respiratory syndrome coronavirus), HAV (Hepatitis A virus), HBV (Hepatitis B virus), HCV (Hepatitis C virus), HIV (human immunodeficiency virus), EBOV (Ebola virus), ZIKV (Zika virus), and most recently SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), are responsible for many diseases that result in hundreds of thousands of deaths yearly. The ongoing outbreak of the COVID-19 disease has raised a global concern and intensified research on the detection of viruses and virus-related diseases. Novel methods for the sensitive, rapid, and on-site detection of pathogens, such as the recent SARS-CoV-2, are critical for diagnosing and treating infectious diseases before they spread and affect human health worldwide. In this sense, electrochemical impedimetric biosensors could be applied for virus detection on a large scale. This review focuses on the recent developments in electrochemical-impedimetric biosensors for the detection of viruses.
Ključne besede: electrochemical impedance spectroscopy, impedimetric biosensor, genosensor, aptasensor, immunosensor, virus detection, SARS-CoV-2, HIV, influenza virus, hepatitis virus
Objavljeno v DKUM: 05.12.2024; Ogledov: 0; Prenosov: 54
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4. COVID-19 vaccine boosters: the good, the bad, and the uglyPiotr Rzymski, Carlos A. Camargo, Andrzej Fal, Robert Flisiak, Willis Gwenzi, Roya Kelishadi, Alexander Leemans, Juan J. Nieto, Ahmet Ozen, Matjaž Perc, Barbara Poniedziałek, Constantine Sedikides, Frank W. Sellke, Emilia C. Skirmuntt, Anzhela Stashchak, Nima Rezaei, 2021, izvirni znanstveni članek Opis: Pursuing vaccinations against COVID-19 brings hope to limit the spread of SARS-CoV-2 and remains the most rational decision under pandemic conditions. However, it does not come without challenges, including temporary shortages in vaccine doses, significant vaccine inequity, and questions regarding the durability of vaccine-induced immunity that remain unanswered. Moreover, SARS-CoV-2 has undergone evolution with the emergence of its novel variants, characterized by enhanced transmissibility and ability to at least partially evade neutralizing antibodies. At the same time, serum antibody levels start to wane within a few months after vaccination, ultimately increasing the risk of breakthrough infections. This article discusses whether the administration of booster doses of COVID-19 vaccines is urgently needed to control the pandemic. We conclude that, at present, optimizing the immunity level of wealthy populations cannot come at the expense of low-income regions that suffer from vaccine unavailability. Although the efficiency of vaccination in protecting from infection may decrease over time, current data show that efficacy against severe disease, hospitalization, and death remains at a high level. If vaccine coverage continues at extremely low levels in various regions, including African countries, SARS-CoV-2 may sooner or later evolve into variants better adapted to evade natural and vaccine-induced immunity, ultimately bringing a global threat that, of course, includes wealthy populations. We offer key recommendations to increase vaccination rates in low-income countries. The pandemic is, by definition, a major epidemiological event and requires looking beyond one's immediate self-interest; otherwise, efforts to contain it will be futile.
Ključne besede: COVID-19, pandemic, disease dynamics, exponential growth, virality, vaccination strategy, immunology, massive vaccinations, vaccine inequity, SARS-CoV-2
Objavljeno v DKUM: 14.10.2024; Ogledov: 0; Prenosov: 10
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5. Factors affecting attitudes towards COVID-19 vaccination : an online survey in SloveniaLuka Petravić, Rok Arh, Tina Gabrovec, Lucija Jazbec, Nika Rupčić, Nina Starešinič, Lea Zorman, Ajda Pretnar Žagar, Andrej Srakar, Matjaž Zwitter, Ana Slavec, 2021, izvirni znanstveni članek Opis: While the problem of vaccine hesitancy is not new, it has become more pronounced with the new COVID-19 vaccines and represents an obstacle to resolving the crisis. Even people who would usually trust vaccines and experts now prefer to wait for more information. A cross-sectional online survey was conducted in Slovenia in December 2020 to find out the attitudes of the population regarding COVID-19 vaccination and the factors that affect these attitudes. Based on 12,042 fully completed questionnaires, we find that higher intention to get vaccinated is associated with men, older respondents, physicians and medical students, respondents who got the influenza vaccination, those who knew someone who had gotten hospitalised or died from COVID-19 and those who have more trust in experts, institutions and vaccines. Nurses and technicians were less likely to get vaccinated. In answers to an open question, sceptics were split into those doubting the quality due to the rapid development of the vaccine and those that reported personal experiences with side effects of prior vaccinations. Although the Slovenian population is diverse in its attitudes towards vaccination, the results are comparable to those found in other countries. However, there are potential limitations to the generalizability of the findings that should be addressed in future studies.
Ključne besede: cross-sectional studies, intention, public opinion, trust, ordinal regression, COVID-19, vaccination, surveys and questionnaires, Europe, immune system, SARS-CoV-2
Objavljeno v DKUM: 10.10.2024; Ogledov: 0; Prenosov: 10
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6. Ukrepi centralne banke za podporo bančnemu sistemu v času pandemije sars - covid - 19Vanesa Fink, 2024, diplomsko delo Opis: Centralna banka je glavna in neodvisna finančna institucija, ki jo ima vsaka država, zato lahko posledično trdimo, da gre za najpomembnejšo finančno institucijo v državi. Zaradi svoje pomembnosti pa centralne banke s svojimi izjavami lahko vplivajo na stanje na finančnem trgu. Glavna naloga centralne banke je, da skrbi za stabilnost gospodarstva države in ga krepi tako, da lahko gospodarstvo raste iz dneva v dan. Centralna banka tudi regulira ponudbo denarja in dostopnost kreditov, ima tudi regulativno funkcijo do določene mere. V letu 2020 pa nas je pretresla novica o pandemiji covid-19, ki ga je 11. marca razglasila Svetovna zdravstvena organizacija (WHO). Gre za novi koronavirus, poimenovan SARS-Cov-2, ki je hud akutni respiratorni sindrom in lahko povzroči resne bolezni. Države v euroobmočju so v ta namen sprejele vrsto ukrepov, da bi preprečile širjenje bolezni. Ena izmed teh ukrepov je bila samoizolacija ljudi in pa ustavitev proizvodnih in poslovnih dejavnosti, kar pa je vodilo k padcu gospodarstva v euroobmočju. V tem letu je v prvi polovici gospodarska aktivnost upadala zaradi ukrepov za omejitev gibanja in povečane nenaklonjenosti tveganju. V drugi polovici pa se je aktivnost nekako stabilizirala ob pomoči močnega in koordiniranega odziva denarne in javnofinančne politike. ECB je v tem času zrahljala naravnanost denarne politike s nabori ukrepov. S tem je nekako preprečila negativen vpliv pandemije v euroobmočju. Angleška centralna banka Bank of England, je v času pandemije znižala obrestno mero na 0,25 odstotka. Za ta ukrep se je banka odločila zato, saj je s tem želela omejiti posledice pandemije, medtem pa je ameriška centralna banka Federal Reserve začela s povišanjem obrestnih mer, in sicer za 0,75 odstotka na 2,25 do 2,50 odstotka. Švedska centralna banka Sveriges Riksbank pa je poleg zniževanju obrestnih mer za banke, dala poudarek na nakupih vrednostnih papirjev, kjer je cilj olajšati dobavo kreditov in ublažiti gospodarstvo.
Ključne besede: centralna banka, tveganje, pandemija SARS-Covid-19, ukrepi, bančni sistem, pravne podlage.
Objavljeno v DKUM: 24.09.2024; Ogledov: 0; Prenosov: 19
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7. Vpliv šoka covida-19 na ameriško gospodarstvo in finančni trgNuša Sluga, 2024, diplomsko delo Opis: V začetku leta 2020 so številne države razglasile izredne razmere, 11. marca 2020 pa je Svetovna zdravstvena organizacija (ang. World Health Organisation, v nadaljevanju WHO) razglasila pandemijo zaradi koronavirusne bolezni covid-19, ki se je konec leta 2019 pojavila v Vuhanu na Kitajskem in se bliskovito razširila na vse celine. Zdravstveni sistem se je soočal z iskanjem načinov testiranja, razvojem cepiva in načinov zdravljenja bolezni, vlade pa so se soočale z iskanjem možnosti za preprečevanje širjenja bolezni in podpore zdravstvenemu sistemu ter gospodarstvu.
V delu diplomskega projekta smo raziskovali vpliv pandemije covida-19 na ameriško gospodarstvo in finančni trg ter ugotovili, da je pandemija covida-19 negativno vplivala tako na ameriško gospodarstvo kot na ameriški finančni trg. Prišlo je do obsežnih odpuščanj, zaradi ukrepov, ki so jih sprejele države. Ti ukrepi so bili začasno prenehanje delovanja podjetji, proizvodnje, storitev, ipd. To je vodilo najprej v recesijo, nato pa v najvišjo inflacijo v maju 2020 v Združenih državah Amerike (v nadaljevanju ZDA). Ameriško gospodarstvo je utrpelo najvišji letni upad bruto domačega proizvoda (v nadaljevanju BDP) po letu 1946, indeksi negotovosti so se zvišali in povzročili zmanjšano potrošnjo prebivalstva in podjetij. Tudi finančni trg je doživel šok, saj so borzni indeksi zelo hitro in rekordno padli. Ukrepi Ameriške centralne banke so vplivali na ponovno rast borznih indeksov, vsak naslednjii val oziroma izbruh pandemije covida-19 pa je povzročil hitrejše okrevanje.
V delu diplomskega projekta smo testirali dve hipotezi in sicer, da je šok covida-19 negativno vplival na ameriško gospodarstvo in da je šok covida-19 negativno vplival na ameriški finančni trg. Obe hipotezi smo potrdili, saj smo ugotovili, da je pandemija negativno vplivala na zaupanje in negotovost med proizvajalci in potrošniki, posledično so rastli indeksi negotovosti, padel je BDP kot posledica upada zasebne in državne potrošnje. Preverjali smo tudi indekse S&P 500, indeks Dow Jones (angleško Dow Jones Industrial Average, v nadaljevanju DJIA) in Nasdaq-100 ter ugotovili, da so največji upad doživeli na začetku pandemije, najverjetneje zaradi povečane skrbi za zdravje in zmanjšanje gospodarske aktivnosti ter črnogledih napovedi. Vsi nadaljnji vali pandemije so na finančne trge vplivali manj, okrevanje pa je bilo hitrejše.
Oblikovalcem politike smo predlagali reformiranje na področju pravočasnega prepoznavanja, preprečevanja in odzivanja na nove izredne situacije, kar bi prispevalo k zmanjšanju negativnih vplivov na zdravstveni in gospodarski sistem.
Ključne besede: Pandemija, covid-19, finančni trgi, gospodarstvo, ameriško gospodarstvo, ameriški finančni trg, SARS-CoV-2.
Objavljeno v DKUM: 05.09.2024; Ogledov: 113; Prenosov: 31
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8. Study of V[sub]2CT[sub]x-MXene Based Immunosensor for Sensitive Label-Free Impedimetric Detection of SARS-CoV-2 Spike ProteinNikola Tasić, Ivan Konjević, Alnilan Cristina Barros Lobato, Dino Metarapi, Matjaž Finšgar, Filipa M. Oliveira, Zdeněk Sofer, Rui Gusmão, Xueji Zhang, Samo B. Hočevar, 2024, izvirni znanstveni članek Opis: Rapid and reliable immunosensing is undoubtedly one of the priorities in the efficient management and combat against a pandemic, as society has experienced with the SARS-CoV-2 outbreak; simple and cost-effective sensing strategies are at the forefront of these efforts. In this regard, 2D-layered MXenes hold great potential for electrochemical biosensing due to their attractive physicochemical properties. Herein, we present a V$_2$CT$_x$ MXene-based sensing layer as an integral part of a label-free immunosensor for sensitive and selective detection of the SARS-CoV-2 spike protein. The sensor was fabricated on a supporting screen-printed carbon electrode using Nafion as an immobilizing agent for MXene and glutaraldehyde, the latter enabling effective binding of protein A for further site-oriented immobilization of anti-SARS-CoV-2 antibodies. A thorough structural analysis of the sensor architecture was carried out, and several key parameters affecting the fabrication and analytical performance of the immunosensor were investigated and optimized. The immunosensor showed excellent electroanalytical performance in combination with an impedimetric approach and exhibited a low detection limit of only 45 fM SARS-CoV-2 spike protein. Its practical applicability was successfully demonstrated by measuring the spike protein in a spiked artificial nasopharyngeal fluid sample.
Ključne besede: imunosenzorji, polprevodniške nanostrukture, proteini, spike protein, immunosensors, SARS-CoV-2, V2CTxMXene
Objavljeno v DKUM: 29.08.2024; Ogledov: 42; Prenosov: 4
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9. COVID-19 vaccination hesitancy among people with chronic neurological disorders : a position paperMartin Rakuša, Serefnur Öztürk, Elena Moro, Raimund Helbok, Claudio Bassetti, Ettore Beghi, Daniel Bereczki, Benedetta Bodini, Giovanni Di Liberto, Tom Jenkins, 2022, izvirni znanstveni članek Opis: Background and purpose
Health risks associated with SARS-CoV-2 infection are undisputed. Moreover, the capability of vaccination to prevent symptomatic, severe, and fatal COVID-19 is recognized. There is also early evidence that vaccination can reduce the chance for long COVID-19. Nonetheless, the willingness to get vaccinated and receive booster shots remains subpar among people with neurologic disorders. Vaccine scepticism not only jeopardizes collective efforts to end the COVID-19 pandemic but puts individual lives at risk, as some chronic neurologic diseases are associated with a higher risk for an unfavorable COVID-19 course.
Methods
In this position paper, the NeuroCOVID-19 Task Force of the European Academy of Neurology (EAN) summarizes the current knowledge on the prognosis of COVID-19 among patients with neurologic disease, elucidates potential barriers to vaccination coverage, and formulates strategies to overcome vaccination hesitancy. A survey among the Task Force members on the phenomenon of vaccination hesitancy among people with neurologic disease supports the lines of argumentation.
Results
The study revealed that people with multiple sclerosis and other nervous system autoimmune disorders are most skeptical of SARS-CoV-2 vaccination. The prevailing concerns included the chance of worsening the pre-existing neurological condition, vaccination-related adverse events, and drug interaction.
Conclusions
The EAN NeuroCOVID-19 Task Force reinforces the key role of neurologists as advocates of COVID-19 vaccination. Neurologists need to argue in the interest of their patients about the overwhelming individual and global benefits of COVID-19 vaccination. Moreover, they need to keep on eye on this vulnerable patient group, its concerns, and the emergence of potential safety signals.
Ključne besede: advocacy, COVID-19, infectious disease prevention, neurological disorders, SARS-CoV-2, vaccination, vaccine skepticism
Objavljeno v DKUM: 02.07.2024; Ogledov: 149; Prenosov: 11
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10. Razvoj au nanodelcev z metodo ultrazvočne razpršilne pirolize za detekcijo protiteles proti SARS-CoV-2 : doktorska disertacijaŽiga Jelen, 2023, doktorska disertacija Opis: V doktorskem delu so predstavljene študije, eksperimentalno delo, tehnike karakterizacije, rezultati in analize, s pomočjo katerih smo potrdili hipotezo, da je možno Au nanodelce (AuND) pripravljene z metodo ultrazvočne razpršilne pirolize (USP), konjugirati s ciljnimi antigeni SARS-CoV-2 in rekombinantnim IgG, da bodo delovali v imunoserološkem hitrem testu na lateralni tok (LFIA), za potrditev potencialne prisotnosti protiteles proti virusu SARS-CoV-2. S ciljno izbranimi parametri (0,5 g/l Au, 5 l/min N2, 2,5 l/min H2) smo z USP sintetizirali AuND iz prekurzorja na osnovi zlatovega (III) klorida. AuND smo zbirali v steklenicah z demineralizirano vodo. Določili smo optimalne stabilizatorje in njihove koncentracije: 2,5 g/L PVP 40K ((C6H9NO)n) ter naknadno dodani 1 g/L trinatrijevega citrata (Na3C6H5O7) in saharoze (C12H22O11), da bi preprečili AuND aglomeracijo. Presevna elektronska mikroskopija AuND je pokazala, da so okrogli, s povprečno velikostjo okoli 50 nm in ozko velikostno porazdelitvijo, brez defektov in nizkim ZETA potencialom, 2,4 mV, pri pH 7,5. Za odstranitev vode iz suspenzije z AuND in stabilizatorji je bila uporabljena liofiliazcija, ki je bila izvedena pri naslednjih pogojih: zamrzovanje pri –40 °C, 4 h, atmosferski tlak; primarno sušenje pri +20 °C, 12 h, 1–4 Pa; sekundarno sušenje pri +30 °C, 33 h, 1–4 Pa. Nastali posušeni AuND so ohranili vse lastnosti, ki so potrebne za funkcijo oznak v hitrih LFIA testih: visoka površinska energija, površinska plazmonska resonanca in proste karboksilne skupine za konjugacijo.
V nadaljevanju izvajanja eksperimentov smo, da bi potrdili doktorske hipoteze, izvedli raziskavo in optimizacijo konjugacije AuND z antigenom SARS-CoV-2, ki je bodičasti protein S1 (ak 1-681), in s protitelesi na zajčji IgG (RMG03). Za določitev poteka konjugacije AuND smo uporabili posredne (gelske elektroforeze, UV-Vis, preizkus delovanja) in direktne (XPS, SIMS) metode. Rezultati so pokazali, da se med našim postopkom konjugacije, v fazah čiščenja odstranimo večinski delež PVP in saharoze, ter s tem sprostimo proste karboksilne funkcionalne skupine citratnih ionov, ki so vezani na povšini AuND. Na teh prostih mestih lahko poteče konjugacija prek prostih -NH2 skupin na proteinih. Njihovo funkcionalnost smo ovrednotili z eksperimentalnimi testiranji lastno razvitega LFIA testa. Na osnovi tega smo postavili model in mehanizem konjugacije AuND, ki predpostavlja, da poteka konjugacija z antigeni oziroma protitelesi prek tvorbe peptidnih vezi med N-koncem proteina in prostimi karboksilnimi skupinami citratnega iona, ki je vezan na površino AuND prek svojih karboksilnih skupin.
Za dodatno potrditev funkcionalizacije AuND z izbranimi biomolekulami smo v sklepnem delu doktorskega dela izvedli klinično študijo na pacientih UKC MB, ki je bila odobrena s sklepom KME RS št. 0120-148/2021/3. Rezultati študije so pokazali, da testi dosegajo visoko občutljivost (83 %) tako na vzorcih nosnega sluza kot na vzorcih seruma, slabšo specifičnost (66 % sluz, 74 % serum), visoko negativno napovedno vrednost (94 %) in slabšo pozitivno napovedno vrednost (38 % sluz, 45 % serum). S študijo smo potrdili delovanje AuND v funkciji oznak, saj so se testne in kontrolne linije v lastno razvitem LFIA hitrem testu obarvale.
Ključne besede: Nanodelci zlata, SARS-CoV-2 virus, stabilizacija, konjugacija, LFIA testi, karakterizacija
Objavljeno v DKUM: 28.03.2024; Ogledov: 347; Prenosov: 61
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