Small Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Fusion by Targeting Cavities on Heptad Repeat Trimers
Mahmoud Kandeel, Mizuki Yamamoto, Abdulla Al‐Taher, Aya Watanabe, Kentaro Oh‐hashi, Byoung Kwon Park, Hyung‐Joo Kwon, Jun‐ichiro Inoue, Mohammed Al‐Nazawi
Abstract
values of 12.6, 21.8, and 11.12 μM, respectively, and were most effective at the onset of spike-receptor interactions. The compounds exhibited safe profiles against Human embryonic kidney cells 293 at a concentration of 20 μM with no observed toxicity in Vero cells at 10 μM. The experimental results are accompanied with predicted favorable pharmacokinetic descriptors and drug-likeness parameters. In conclusion, this study provides the first generation of MERS-CoV fusion inhibitors with potencies in the low micromolar range.
Topics & Concepts
Middle East respiratory syndrome coronavirusVero cellHeptad repeatIC50Virtual screeningMiddle East respiratory syndromeDrug discoveryFusionPharmacokineticsFusion proteinCoronavirus disease 2019 (COVID-19)ReceptorVirologySmall moleculeChemistryPharmacologyIn vitroBiologyMedicineVirusBiochemistryDiseasePeptide sequenceInternal medicineRecombinant DNAInfectious disease (medical specialty)GeneLinguisticsPhilosophySARS-CoV-2 and COVID-19 ResearchComputational Drug Discovery Methodsvaccines and immunoinformatics approaches