TY - JOUR
AU - Bardiot, Dorothée
AU - Vangeel, Laura
AU - Koukni, Mohamed
AU - Arzel, Philippe
AU - Zwaagstra, Marleen
AU - Lyoo, Heyrhyoung
AU - Wanningen, Patrick
AU - Ahmad, Shamshad
AU - Zhang, Linlin
AU - Sun, Xinyuanyuan
AU - Delpal, Adrien
AU - Eydoux, Cecilia
AU - Guillemot, Jean-Claude
AU - Lescrinier, Eveline
AU - Klaassen, Hugo
AU - Leyssen, Pieter
AU - Jochmans, Dirk
AU - Castermans, Karolien
AU - Hilgenfeld, Rolf
AU - Robinson, Colin
AU - Decroly, Etienne
AU - Canard, Bruno
AU - Snijder, Eric J.
AU - van Hemert, Martijn J.
AU - van Kuppeveld, Frank J.
AU - Chaltin, Patrick
AU - Neyts, Johan
AU - De Jonghe, Steven
AU - Marchand, Arnaud
PY - 2022
DA - February
TI - Synthesis, Structure–Activity Relationships, and Antiviral Profiling of 1-Heteroaryl-2-Alkoxyphenyl Analogs as Inhibitors of SARS-CoV-2 Replication
JO - Molecules
VL - 27
IS - 3
DO - https://doi.org/10.3390/molecules27031052
AB - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has led to a pandemic, that continues to be a huge public health burden. Despite the availability of vaccines, there is still a need for small-molecule antiviral drugs. In an effort to identify novel and drug-like hit matter that can be used for subsequent hit-to-lead optimization campaigns, we conducted a high-throughput screening of a 160 K compound library against SARS-CoV-2, yielding a 1-heteroaryl-2-alkoxyphenyl analog as a promising hit. Antiviral profiling revealed this compound was active against various beta-coronaviruses and preliminary mode-of-action experi-ments demonstrated that it interfered with viral entry. A systematic structure–activity relationship (SAR) study demonstrated that a 3-or 4-pyridyl moiety on the oxadiazole moiety is optimal, whereas the oxadiazole can be replaced by various other heteroaromatic cycles. In addition, the alkoxy group tolerates some structural diversity.
PB - MDPI
UR - https://discovery.dundee.ac.uk/en/publications/370ae08f-3c0b-4f2b-95d3-fa25886f8181
KW - Coronavirus (COVID-19)
ER