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bioRxiv · 10.1101/2020.07.10.197988

Identifying SARS-CoV-2 entry inhibitors through drug repurposing screens of SARS- S and MERS-S pseudotyped particles

Catherine Z. Chen·Miao Xu·Manisha Pradhan·Kirill Gorshkov·Jennifer Petersen·Marco R. Straus·Wei Zhu·Paul Shinn·Hui Guo·Min Shen·Carleen Klumpp-Thomas·Samuel G. Michael·Joshua Zimmerberg·Wei Zheng·Gary R Whittaker
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Abstract

While vaccine development will hopefully quell the global pandemic of COVID-19 caused by SARS-CoV-2, small molecule drugs that can effectively control SARS-CoV-2 infection are urgently needed. Here, inhibitors of spike (S) mediated cell entry were identified in a high throughput screen of an approved drugs library with SARS-S and MERS-S pseudotyped particle entry assays. We discovered six compounds (cepharanthine, abemaciclib, osimertinib, trimipramine, colforsin, and ingenol) to be broad spectrum inhibitors for spike-mediated entry. This work should contribute to the development of effective treatments against the initial stage of viral infection, thus reducing viral burden in COVID-19 patients. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/197988v2_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@d60124org.highwire.dtl.DTLVardef@1e5152dorg.highwire.dtl.DTLVardef@d16655org.highwire.dtl.DTLVardef@1957bcc_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Catherine Z. Chen, Miao Xu, Manisha Pradhan, Kirill Gorshkov, Jennifer Petersen, Marco R. Straus, Wei Zhu, Paul Shinn, Hui Guo, Min Shen, Carleen Klumpp-Thomas, Samuel G. Michael, Joshua Zimmerberg, Wei Zheng, Gary R Whittaker. 2020-07-11. Identifying SARS-CoV-2 entry inhibitors through drug repurposing screens of SARS- S and MERS-S pseudotyped particles. https://doi.org/10.1101/2020.07.10.197988

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