The Dual-Targeted Fusion Inhibitor Clofazimine Binds to the S2 Segment of the SARS-CoV-2 Spike Protein DOI Open Access

Matthew R. Freidel,

Pratiti A. Vakhariya,

Shalinder K. Sardarni

et al.

Published: March 4, 2024

Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs repurposed for treatment of COVID-19 used several previous ongoing clinical trials. Small-molecule binding expressed constructs the trimeric S2 segment Spike full-length spike protein were measured using a Surface Plasmon Resonance (SPR) assay. We demonstrate that Clofazimine, Toremifene, other derivatives bind protein. provided most reliable highest quality SPR data over conditions explored. A molecular docking approach was identify favorable sites on prefusion conformation, highlighting two possible small-molecule Results from modeling structure-activity-relationship (SAR) newly series supports proposed site segment. When is superimposed with experimentally determined coronavirus structures structure-sequence alignments, changes sequence structure may rationalize broad-spectrum antiviral activity closely related such as (SARS-CoV, MERS, hCoV-229E, hCoV-OC43).

Language: Английский

The Dual-Targeted Fusion Inhibitor Clofazimine Binds to the S2 Segment of the SARS-CoV-2 Spike Protein DOI Open Access

Matthew R. Freidel,

Pratiti A. Vakhariya,

Shalinder K. Sardarni

et al.

Published: March 4, 2024

Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs repurposed for treatment of COVID-19 used several previous ongoing clinical trials. Small-molecule binding expressed constructs the trimeric S2 segment Spike full-length spike protein were measured using a Surface Plasmon Resonance (SPR) assay. We demonstrate that Clofazimine, Toremifene, other derivatives bind protein. provided most reliable highest quality SPR data over conditions explored. A molecular docking approach was identify favorable sites on prefusion conformation, highlighting two possible small-molecule Results from modeling structure-activity-relationship (SAR) newly series supports proposed site segment. When is superimposed with experimentally determined coronavirus structures structure-sequence alignments, changes sequence structure may rationalize broad-spectrum antiviral activity closely related such as (SARS-CoV, MERS, hCoV-229E, hCoV-OC43).

Language: Английский

Citations

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