20.500.12556/DiRROS-20177 Identification of triazolopyrimidinyl scaffold SARS-CoV-2 papain-like protease (PLpro) inhibitor The global impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its companion disease, COVID-19, has reminded us of the importance of basic coronaviral research. In this study, a comprehensive approach using molecular docking, in vitro assays, and molecular dynamics simulations was applied to identify potential inhibitors for SARS-CoV-2 papain-like protease (PLpro), a key and underexplored viral enzyme target. A focused protease inhibitor library was initially created and molecular docking was performed using CmDock software (v0.2.0), resulting in the selection of hit compounds for in vitro testing on the isolated enzyme. Among them, compound 372 exhibited promising inhibitory properties against PLpro, with an IC50 value of 82 ± 34 μM. The compound also displayed a new triazolopyrimidinyl scaffold not yet represented within protease inhibitors. Molecular dynamics simulations demonstrated the favorable binding properties of compound 372. Structural analysis highlighted its key interactions with PLpro, and we stress its potential for further optimization. Moreover, besides compound 372 as a candidate for PLpro inhibitor development, this study elaborates on the PLpro binding site dynamics and provides a valuable contribution for further efforts in pan-coronaviral PLpro inhibitor development. drug design protease inhibitor SARS-CoV-2 papain-like protease PLpro antiviral design in silico drug design CADD virtual screening HTVS structure-based design zdravila inhibitorji proteaze proteaza true false true Angleški jezik Slovenski jezik Neznano 2024-08-07 11:06:07 2024-08-07 11:06:07 2024-08-08 04:07:53 0000-00-00 00:00:00 2024 0 0 Nasl. z nasl. zaslona; Soavtorji: Marko Jukič, Miha Bahun, Luka Kranjc, Anja Kolarič, Milan Hodošček, Nataša Poklar Ulrih, Urban Bren; Opis vira z dne 26. 1. 2024; 13 str. issue 2, [article no.] 169 Vol. 16 Feb. 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2024-01-25 60:543.2/.9 1999-4923 10.3390/pharmaceutics16020169 182627331 https://dk.um.si/IzpisGradiva.php?id=86901 1 902ea114-548b-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=28214 RAZ_Kralj_Sebastjan_2024.pdf RAZ_Kralj_Sebastjan_2024.pdf 1 CA3191C422FA5AF327E58194FCEA67DE be27b151ccba83f98807bf461294a1f6a0008b9bbc511c272e338283f4017f4b cd74cb55-548b-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=28215 https://doi.org/10.3390/pharmaceutics16020169 0 d4db943e-548b-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=28216 Nacionalni inštitut za biologijo 0 0 0