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Query: "author" (Roman Jerala) .

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TXM peptides inhibit SARS-CoV-2 infection, syncytia formation, and lower inflamatory consequences
Tea Govednik, Duško Lainšček, Urška Kuhar, Marva Lachish, Sandra Janežič, Malan Štrbenc, Uroš Krapež, Roman Jerala, Daphne Atlas, Mateja Manček Keber, 2024, original scientific article

Abstract: After three years of the SARS-CoV-2 pandemic, the search and availability of relatively low-cost benchtop therapeutics for people not at high risk for a severe disease are still ongoing. Although vaccines and new SARS-CoV-2 variants reduce the death toll, the long COVID-19 along with neurologic symptoms can develop and persist even after a mild initial infection. Reinfections, which further increase the risk of sequelae in multiple organ systems as well as the risk of death, continue to require caution. The spike protein of SARS-CoV-2 is an important target for both vaccines and therapeutics. The presence of disulfide bonds in the receptor binding domain (RBD) of the spike protein is essential for its binding to the human ACE2 receptor and cell entry. Here, we demonstrate that thiol-reducing peptides based on the active site of oxidoreductase thioredoxin 1, called thioredoxin mimetic (TXM) peptides, can prevent syncytia formation, SARS-CoV-2 entry into cells, and infection in a mouse model. We also show that TXM peptides inhibit the redox-sensitive HIV pseudotyped viral cell entry. These results support disulfide targeting as a common therapeutic strategy for treating infections caused by viruses using redox-sensitive fusion. Furthermore, TXM peptides exert anti-inflammatory properties by lowering the activation of NF-κB and IRF signaling pathways, mitogen-activated protein kinases (MAPKs) and lipopolysaccharide (LPS)-induced cytokines in mice. The antioxidant and anti-inflammatory effects of the TXM peptides, which also cross the blood-brain barrier, in combination with prevention of viral infections, may provide a beneficial clinical strategy to lower viral infections and mitigate severe consequences of COVID-19.
Keywords: SARS-CoV-2, Disulfides, Thiol-reacting compound, Spike, Anti-inflammatory activity
Published in DiRROS: 06.02.2024; Views: 240; Downloads: 104
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Crystal structure of de novo designed coiled-coil protein origami triangle
Tadej Satler, San Hadži, Roman Jerala, 2023, original scientific article

Published in DiRROS: 26.10.2023; Views: 495; Downloads: 181
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Engineered combinatorial cell device for wound healing and bone regeneration
Lucija Kadunc, Duško Lainšček, Rok Gašperšič, Petra Sušjan, Uroš Kovačič, Miha Butinar, Boris Turk, Roman Jerala, Iva Hafner Bratkovič, 2023, original scientific article

Abstract: Growth factors are the key regulators that promote tissue regeneration and healing processes. While the effects of individual growth factors are well documented, a combination of multiple secreted growth factors underlies stem cell–mediated regeneration. To avoid the potential dangers and laborintensive individual approach of stem cell therapy while maintaining their regeneration-promoting effects based on multiple secreted growth factors, we engineered a “mix-and-match” combinatorial platform based on a library of cell lines producing growth factors. Treatment with a combination of growth factors secreted by engineered mammalian cells was more efficient than with individual growth factors or even stem cell–conditioned medium in a gap closure assay. Furthermore, we implemented in a mouse model a device for allogenic cell therapy for an in situ production of growth factors, where it improved cutaneous wound healing. Augmented bone regeneration was achieved on calvarial bone defects in rats treated with a cell device secreting IGF, FGF, PDGF, TGF-β, and VEGF. In both in vivo models, the systemic concentration of secreted factors was negligible, demonstrating the local effect of the regeneration device. Finally, we introduced a genetic switch that enables temporal control over combinations of trophic factors released at different stages of regeneration mimicking the maturation of natural wound healing to improve therapy and prevent scar formation.
Keywords: wound healing, bone regeneration, growth factors
Published in DiRROS: 01.06.2023; Views: 533; Downloads: 209
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Coiled coils as versatile modules for mammalian cell regulation
Estera Merljak, Anja Golob Urbanc, Tjaša Plaper, Roman Jerala, 2023, review article

Published in DiRROS: 26.05.2023; Views: 531; Downloads: 175
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Segmentation strategy of de novo designed four-helical bundles expands protein oligomerization modalities for cell regulation
Estera Merljak, Benjamin Malovrh, Roman Jerala, 2023, original scientific article

Published in DiRROS: 26.04.2023; Views: 529; Downloads: 211
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Proteolytically activated CRAC effectors through designed intramolecular inhibition
Vid Jazbec, Roman Jerala, Mojca Benčina, 2022, original scientific article

Keywords: STIM1, Orai, TEV protease, PPV protease, calcium signaling, coiled-coil peptides
Published in DiRROS: 20.07.2022; Views: 719; Downloads: 425
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Designed protease-based signaling networks
Roman Jerala, Tina Fink, 2022, original scientific article

Keywords: proteolysis, viral proteases, endogenous proteases, protease-based sensors, synthetic signaling cascades
Published in DiRROS: 20.05.2022; Views: 717; Downloads: 471
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Robust saliva-based RNA extraction-free one-step nucleic acid amplification test for mass SARS-CoV-2 monitoring
Eva Rajh, Tina Šket, Arne Praznik, Petra Sušjan, Alenka Šmid, Dunja Urbančič, Irena Mlinarič-Raščan, Polona Kogovšek, Tina Demšar, Mojca Milavec, Katarina Prosenc, Žiga Jensterle, Mihaela Zidarn, Viktorija Tomič, Gabriele Turel, Tatjana Lejko-Zupanc, Roman Jerala, Mojca Benčina, 2021, original scientific article

Abstract: Early diagnosis with rapid detection of the virus plays a key role in preventing the spread of infection and in treating patients effectively. In order to address the need for a straightforward detection of SARS-CoV-2 infection and assessment of viral spread, we developed rapid, sensitive, extraction-free one-step reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and reverse transcription loop-mediated isothermal amplification (RT-LAMP) tests for detecting SARS-CoV-2 in saliva. We analyzed over 700 matched pairs of saliva and nasopharyngeal swab (NSB) specimens from asymptomatic and symptomatic individuals. Saliva, as either an oral cavity swab or passive drool, was collected in an RNA stabilization buffer. The stabilized saliva specimens were heat-treated and directly analyzed without RNA extraction. The diagnostic sensitivity of saliva-based RT-qPCR was at least 95% in individuals with subclinical infection and outperformed RT-LAMP, which had at least 70% sensitivity when compared to NSBs analyzed with a clinical RT-qPCR test. The diagnostic sensitivity for passive drool saliva was higher than that of oral cavity swab specimens (95% and 87%, respectively). A rapid, sensitive one-step extraction-free RT-qPCR test for detecting SARS-CoV-2 in passive drool saliva is operationally simple and can be easily implemented using existing testing sites, thus allowing high-throughput, rapid, and repeated testing of large populations. Furthermore, saliva testing is adequate to detect individuals in an asymptomatic screening program and can help improve voluntary screening compliance for those individuals averse to various forms of nasal collections.
Keywords: SARS-CoV-2, COVID-19, COVID-19 serological testing, real-time polymerase chain reaction, saliva, oral cavity swab, passive drool, pooling
Published in DiRROS: 09.11.2021; Views: 1134; Downloads: 558
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Triangular in vivo self-assembling coiled-coil protein origami
Sabina Božič Abram, Helena Gradišar, Jana Aupič, Adam Round, Roman Jerala, 2021, original scientific article

Keywords: coiled coil, enzyme clustering, biosynthesis, resveratrol, mevalonate
Published in DiRROS: 22.03.2021; Views: 1492; Downloads: 921
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