Rapid discovery and classification of inhibitors of coronavirus infection by pseudovirus screen and amplified luminescence proximity homogeneous assay
Antiviral Res. 2022 Nov 23:105473. doi: 10.1016/j.antiviral.2022.105473. Online ahead of print.ABSTRACTTo identify potent antiviral compounds, we introduced a high-throughput screen platform that can rapidly classify hit compounds according to their target. In our platform, we performed a compound screen using a lentivirus-based pseudovirus presenting a spike protein of coronavirus, and we evaluated the hit compounds using an amplified luminescence proximity homogeneous assay (alpha) test with purified host receptor protein and the receptor binding domain of the viral spike. With our screen platform, we were able to identify both spike-specific compounds (class I) and broad-spectrum antiviral compounds (class II). Among the hit compounds, thiosemicarbazide was identified to be selective to the interaction between the viral spike and its host cell receptor, and we further optimized the binding potency of thiosemicarbazide through modification of the pyridine group. Among the class II compounds, we found raloxifene and amiodarone to be highly potent against human coronaviruses including Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and SARS-CoV-2. In particular, using analogs of the benzothiophene moiety, which is also present in raloxifene, we have identified benzothiophene as a novel structural scaffold for broad-spectrum antivirals. This work highlights the strong utility of our screen platform using a pseu...
Source: Cell Research - Category: Cytology Authors: Kwiwan Jeong JuOae Chang Sun-Mi Park Jinhee Kim Sangeun Jeon Dong Hwan Kim Young-Eui Kim Joo Chan Lee Somyoung Im Yejin Jo Ji-Young Min Hanbyeul Lee Minjoo Yeom Sang-Hyuk Seok Da In On Hyuna Noh Jun-Won Yun Jun Won Park Daesub Song Je Kyung Seong Kyung-Ch Source Type: research
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