@article{MTMT:34557141,
	title = {The Design, Synthesis and Mechanism of Action of Paxlovid, a Protease Inhibitor Drug Combination for the Treatment of COVID-19},
	url = {https://m2.mtmt.hu/api/publication/34557141},
	author = {Bege, Miklós and Borbás, Anikó},
	doi = {10.3390/pharmaceutics16020217},
	journal-iso = {PHARMACEUTICS},
	journal = {PHARMACEUTICS},
	volume = {16},
	unique-id = {34557141},
	issn = {1999-4923},
	abstract = {The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented an enormous challenge to health care systems and medicine. As a result of global research efforts aimed at preventing and effectively treating SARS-CoV-2 infection, vaccines with fundamentally new mechanisms of action and some small-molecule antiviral drugs targeting key proteins in the viral cycle have been developed. The most effective small-molecule drug approved to date for the treatment of COVID-19 is PaxlovidTM, which is a combination of two protease inhibitors, nirmatrelvir and ritonavir. Nirmatrelvir is a reversible covalent peptidomimetic inhibitor of the main protease (Mpro) of SARS-CoV-2, which enzyme plays a crucial role in viral reproduction. In this combination, ritonavir serves as a pharmacokinetic enhancer, it irreversibly inhibits the cytochrome CYP3A4 enzyme responsible for the rapid metabolism of nirmatrelvir, thereby increasing the half-life and bioavailability of nirmatrelvir. In this tutorial review, we summarize the development and pharmaceutical chemistry aspects of Paxlovid, covering the evolution of protease inhibitors, the warhead design, synthesis and the mechanism of action of nirmatrelvir, as well as the synthesis of ritonavir and its CYP3A4 inhibition mechanism. The efficacy of Paxlovid to novel virus mutants is also overviewed.},
	year = {2024},
	eissn = {1999-4923},
	orcid-numbers = {Borbás, Anikó/0000-0001-8462-4547}
}

@article{MTMT:34863210,
	title = {Paxlovid: proteázgátló kombináció SARS-CoV-2 ellen},
	url = {https://m2.mtmt.hu/api/publication/34863210},
	author = {Bege, Miklós},
	journal-iso = {GYÓGYSZERÉSZET},
	journal = {GYÓGYSZERÉSZET},
	volume = {LXVII},
	unique-id = {34863210},
	issn = {0017-6036},
	year = {2023},
	pages = {19-22}
}

@article{MTMT:34081319,
	title = {In vitro and in vivo antiplasmodial evaluation of sugar-modified nucleoside analogues},
	url = {https://m2.mtmt.hu/api/publication/34081319},
	author = {Bege, Miklós and Singh, Vigyasa and Sharma, Neha and Debreczeni, Nóra and Bakai-Bereczki, Ilona and Nam, Poo and Herczegh, Pál and Rathi, Brijesh and Singh, Shailja and Borbás, Anikó},
	doi = {10.1038/s41598-023-39541-4},
	journal-iso = {SCI REP},
	journal = {SCIENTIFIC REPORTS},
	volume = {13},
	unique-id = {34081319},
	issn = {2045-2322},
	abstract = {Drug-resistant Plasmodium falciparum ( Pf ) infections are a major burden on the population and the healthcare system. The establishment of Pf resistance to most existing antimalarial therapies has complicated the problem, and the emergence of resistance to artemisinin derivatives is even more concerning. It is increasingly difficult to cure malaria patients due to the limited availability of effective antimalarial drugs, resulting in an urgent need for more efficacious and affordable treatments to eradicate this disease. Herein, new nucleoside analogues including morpholino-nucleoside hybrids and thio-substituted nucleoside derivatives were prepared and evaluated for in vitro and in vivo antiparasitic activity that led a few hits especially nucleoside-thiopyranoside conjugates, which are highly effective against Pf 3D7 and Pf RKL-9 strains in submicromolar concentration. One adenosine derivative and four pyrimidine nucleoside analogues significantly reduced the parasite burden in mouse models infected with Plasmodium berghei ANKA. Importantly, no significant hemolysis and cytotoxicity towards human cell line (RAW) was observed for the hits, suggesting their safety profile. Preliminary research suggested that these thiosugar-nucleoside conjugates could be used to accelerate the antimalarial drug development pipeline and thus deserve further investigation.},
	year = {2023},
	eissn = {2045-2322},
	orcid-numbers = {Bakai-Bereczki, Ilona/0000-0003-4601-7257; Borbás, Anikó/0000-0001-8462-4547}
}

@article{MTMT:33802561,
	title = {Allosteric regulation and crystallographic fragment screening of SARS-CoV-2 NSP15 endoribonuclease},
	url = {https://m2.mtmt.hu/api/publication/33802561},
	author = {Godoy, Andre Schutzer and Nakamura, Aline Minalli and Douangamath, Alice and Song, Yun and Noske, Gabriela Dias and Gawriljuk, Victor Oliveira and Fernandes, Rafaela Sachetto and Pereira, Humberto D Muniz and Oliveira, Ketllyn Irene Zagato and Fearon, Daren and Dias, Alexandre and Krojer, Tobias and Fairhead, Michael and Powell, Alisa and Dunnet, Louise and Brandao-Neto, Jose and Skyner, Rachael and Chalk, Rod and Bajusz, Dávid and Bege, Miklós and Borbás, Anikó and Keserű, György Miklós and von Delft, Frank and Oliva, Glaucius},
	doi = {10.1093/nar/gkad314},
	journal-iso = {NUCLEIC ACIDS RES},
	journal = {NUCLEIC ACIDS RESEARCH},
	volume = {51},
	unique-id = {33802561},
	issn = {0305-1048},
	abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). The NSP15 endoribonuclease enzyme, known as NendoU, is highly conserved and plays a critical role in the ability of the virus to evade the immune system. NendoU is a promising target for the development of new antiviral drugs. However, the complexity of the enzyme's structure and kinetics, along with the broad range of recognition sequences and lack of structural complexes, hampers the development of inhibitors. Here, we performed enzymatic characterization of NendoU in its monomeric and hexameric form, showing that hexamers are allosteric enzymes with a positive cooperative index, and with no influence of manganese on enzymatic activity. Through combining cryo-electron microscopy at different pHs, X-ray crystallography and biochemical and structural analysis, we showed that NendoU can shift between open and closed forms, which probably correspond to active and inactive states, respectively. We also explored the possibility of NendoU assembling into larger supramolecular structures and proposed a mechanism for allosteric regulation. In addition, we conducted a large fragment screening campaign against NendoU and identified several new allosteric sites that could be targeted for the development of new inhibitors. Overall, our findings provide insights into the complex structure and function of NendoU and offer new opportunities for the development of inhibitors.},
	year = {2023},
	eissn = {1362-4962},
	pages = {5255-5270},
	orcid-numbers = {Godoy, Andre Schutzer/0000-0002-0613-9164; Bajusz, Dávid/0000-0003-4277-9481; Borbás, Anikó/0000-0001-8462-4547; von Delft, Frank/0000-0003-0378-0017}
}

@article{MTMT:33657380,
	title = {Triaza-tricyclanos – synthesis of a new class of tricyclic nucleoside analogues by stereoselective cascade cyclocondensation},
	url = {https://m2.mtmt.hu/api/publication/33657380},
	author = {Bege, Miklós and Herczeg, Mihály and Bakai-Bereczki, Ilona and Debreczeni, Nóra and Bényei, Attila Csaba and Herczegh, Pál and Borbás, Anikó},
	doi = {10.1039/D3OB00154G},
	journal-iso = {ORG BIOMOL CHEM},
	journal = {ORGANIC & BIOMOLECULAR CHEMISTRY},
	volume = {21},
	unique-id = {33657380},
	issn = {1477-0520},
	abstract = {Conformationally constrained tricyclic morpholino-nucleosides containing three new chirality centers were prepared with full stereoselectivity, through two consecutive hemiaminal-imidazolidine cascade reactions.},
	year = {2023},
	eissn = {1477-0539},
	pages = {2213-2219},
	orcid-numbers = {Herczeg, Mihály/0000-0002-7938-9789; Bakai-Bereczki, Ilona/0000-0003-4601-7257; Borbás, Anikó/0000-0001-8462-4547}
}

@article{MTMT:33297309,
	title = {N‐Fluoroalkylated Morpholinos – a New Class of Nucleoside Analogues},
	url = {https://m2.mtmt.hu/api/publication/33297309},
	author = {Debreczeni, Nóra and Hotzi, Judit and Bege, Miklós and Lovas, Miklós and Mező, Erika and Bakai-Bereczki, Ilona and Herczegh, Pál and Kiss, Loránd and Borbás, Anikó},
	doi = {10.1002/chem.202203248},
	journal-iso = {CHEM-EUR J},
	journal = {CHEMISTRY-A EUROPEAN JOURNAL},
	volume = {29},
	unique-id = {33297309},
	issn = {0947-6539},
	year = {2023},
	eissn = {1521-3765},
	orcid-numbers = {Mező, Erika/0000-0002-8329-6745; Bakai-Bereczki, Ilona/0000-0003-4601-7257; Herczegh, Pál/0000-0003-4265-5518; Kiss, Loránd/0000-0003-2346-9816; Borbás, Anikó/0000-0001-8462-4547}
}

@article{MTMT:34863208,
	title = {Géncsendesítő gyógyszerek IV. Az RNS-interferencia felhasználása a gyógyászatban},
	url = {https://m2.mtmt.hu/api/publication/34863208},
	author = {Bege, Miklós},
	journal-iso = {GYÓGYSZERÉSZET},
	journal = {GYÓGYSZERÉSZET},
	volume = {LXVI},
	unique-id = {34863208},
	issn = {0017-6036},
	year = {2022},
	pages = {628-632}
}

@article{MTMT:34863207,
	title = {Géncsendesítő gyógyszerek III. Splicing moduláló oligonukleotidok},
	url = {https://m2.mtmt.hu/api/publication/34863207},
	author = {Bege, Miklós},
	journal-iso = {GYÓGYSZERÉSZET},
	journal = {GYÓGYSZERÉSZET},
	volume = {LXVI},
	unique-id = {34863207},
	issn = {0017-6036},
	year = {2022},
	pages = {584-588}
}

@article{MTMT:33663027,
	title = {Nukleozidanalóg hatóanyagok használata a Covid-19 kezelésére},
	url = {https://m2.mtmt.hu/api/publication/33663027},
	author = {Bege, Miklós},
	journal-iso = {GYÓGYSZERÉSZET},
	journal = {GYÓGYSZERÉSZET},
	volume = {66},
	unique-id = {33663027},
	issn = {0017-6036},
	year = {2022},
	pages = {232-235}
}

@article{MTMT:33663026,
	title = {Géncsendesítő gyógyszerek I. - Bevezetés a természetes és mesterséges nukleinsavak világába},
	url = {https://m2.mtmt.hu/api/publication/33663026},
	author = {Bege, Miklós},
	journal-iso = {GYÓGYSZERÉSZET},
	journal = {GYÓGYSZERÉSZET},
	volume = {66},
	unique-id = {33663026},
	issn = {0017-6036},
	year = {2022},
	pages = {395-400}
}