20.500.12556/DKUM-92745 Novel small-molecule inhibitors of the SARS-CoV-2 spike protein binding to neuropilin 1 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. neuropilin 1 SARS-CoV-2 COVID-19 spike binding inhibitors virtual screening small-molecule antagonists molecular docking in vitro binding assay inhibitorji molekule true false true MDPI, Molecular Diversity Preservation International Angleški jezik Slovenski jezik https://www.mdpi.com/journal/pharmaceuticals © 2022 by the authors Članek v reviji 2025-05-09 13:26:06 2025-05-09 13:26:06 2025-05-10 03:10:00 0000-00-00 00:00:00 2022 0 0 14 str. no. 2 Vol. 15 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2021-10-29 2022-01-26 2022-01-28 577 95574275 10.3390/ph15020165 1424-8247 pharmaceuticals-15-00165-v2.pdf pharmaceuticals-15-00165-v2.pdf 1 B82CA77FA0906A8506807CA8247AE1BD 6d6c3bee8bc8792c47d402fa8da3eea7b88d8d925b7450969ae4d4258826c5c5 e09e1987-2cc8-11f0-acfb-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=190839 https://www.mdpi.com/1424-8247/15/2/165 0 e923525f-2cc8-11f0-acfb-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=190840 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0