Furin Inhibitors Block SARS-CoV-2 Spike Protein Cleavage to Suppress Virus Production and Cytopathic Effects

• DOI: 10.1016/j.celrep.2020.108254
• Publication Date: 2020-09-23T16:33:17Z
• Authors: Ya-Wen Cheng; Tai-Ling Chao; Chiao-Ling Li; Mu-Fan Chiu; Han-Chieh Kao; Sheng-Han Wang; Yu-Hao Pang; Chih-Hui Lin; Ya-Min Tsai; Wen-Hau Lee; Mi-Hua Tao; Tung-Ching Ho; Ping-Yi Wu; Li-Ting Jang; Pei-Jer Chen; Sui-Yuan Chang; Shiou-Hwei Yeh
• Keywords: Furin; Syncytium; Coronavirus; Cleavage (geology); TMPRSS2; Cytopathic effect

Development of specific antiviral agents is an urgent unmet need for SARS-coronavirus 2 (SARS-CoV-2) infection. This study focuses on host proteases that proteolytically activate the SARS-CoV-2 spike protein, critical its fusion after binding to angiotensin-converting enzyme (ACE2), as targets. We first validate cleavage at a putative furin substrate motif spikes by expressing it in VeroE6 cells and find prominent syncytium formation. Cleavage are abolished treatment with inhibitors decanoyl-RVKR-chloromethylketone (CMK) naphthofluorescein, but not transmembrane protease serine (TMPRSS2) inhibitor camostat. CMK naphthofluorescein show effects SARS-CoV-2-infected decreasing virus production cytopathic effects. Further analysis reveals that, similar camostat, blocks entry, further suppresses syncytium. Naphthofluorescein acts primarily suppressing viral RNA transcription. Therefore, may be promising prevention