Research Progress on Spike-Dependent SARS CoV-2 Fusion Inhibitors and Small Molecules Targeting the S2 Subunit of Spike DOI Open Access

Matthew R. Freidel,

Roger S. Armen

Published: March 4, 2024

Since the beginning of COVID-19 pandemic, extensive drug repurposing efforts sought to identify small molecule antivirals with various mechanisms action. Here we aim review research progress on viral entry and fusion inhibitors that directly bind SARS CoV-2 Spike protein. Early in numerous molecules were identified screens reported be effective vitro or inhibitors. However, given minimal experimental information regarding exact location binding sites Spike, it was unclear what specific mechanism action was, where for some inhibitor candidates. The work countless researchers has yielded great progress, identification many target elements S1 receptor domain (RBD) N-terminal (NTD) disrupt function. In this review, will also focus highlighting inhibition S2 function, either by disrupting formation postfusion conformation alternatively stabilizing structural prefusion prevent conformational changes associated We highlight experimentally validated S1/S2 interface subunit. While most mutations protein date variants concern (VOCs) have been localized subunit, subunit sequence is more conserved only a few observed proximity sites. Several recent targeting shown robust activity over VOC mutant strains and/or greater broad spectrum antiviral other distantly related coronaviruses.

Language: Английский

Research Progress on Spike-Dependent SARS CoV-2 Fusion Inhibitors and Small Molecules Targeting the S2 Subunit of Spike DOI Open Access

Matthew R. Freidel,

Roger S. Armen

Published: March 4, 2024

Since the beginning of COVID-19 pandemic, extensive drug repurposing efforts sought to identify small molecule antivirals with various mechanisms action. Here we aim review research progress on viral entry and fusion inhibitors that directly bind SARS CoV-2 Spike protein. Early in numerous molecules were identified screens reported be effective vitro or inhibitors. However, given minimal experimental information regarding exact location binding sites Spike, it was unclear what specific mechanism action was, where for some inhibitor candidates. The work countless researchers has yielded great progress, identification many target elements S1 receptor domain (RBD) N-terminal (NTD) disrupt function. In this review, will also focus highlighting inhibition S2 function, either by disrupting formation postfusion conformation alternatively stabilizing structural prefusion prevent conformational changes associated We highlight experimentally validated S1/S2 interface subunit. While most mutations protein date variants concern (VOCs) have been localized subunit, subunit sequence is more conserved only a few observed proximity sites. Several recent targeting shown robust activity over VOC mutant strains and/or greater broad spectrum antiviral other distantly related coronaviruses.

Language: Английский

Citations

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