tetano
Editor, Senior Moderator
iScience
. 2024 May 17;27(6):110019.
doi: 10.1016/j.isci.2024.110019. eCollection 2024 Jun 21. High-throughput screening identifies broad-spectrum Coronavirus entry inhibitors
Suman Khan[SUP] 1 [/SUP], Efrat Ozer Partuk[SUP] 1 [/SUP], Jeanne Chiaravalli[SUP] 2 [/SUP], Noga Kozer[SUP] 3 [/SUP], Khriesto A Shurrush[SUP] 3 [/SUP], Yael Elbaz-Alon[SUP] 1 [/SUP], Nadav Scher[SUP] 1 [/SUP], Emilie Giraud[SUP] 2 [/SUP], Jaouen Tran-Rajau[SUP] 2 [/SUP], Fabrice Agou[SUP] 2 [/SUP], Haim Michael Barr[SUP] 3 [/SUP], Ori Avinoam[SUP] 1 [/SUP]
Affiliations
The COVID-19 pandemic highlighted the need for antivirals against emerging coronaviruses (CoV). Inhibiting spike (S) glycoprotein-mediated viral entry is a promising strategy. To identify small molecule inhibitors that block entry downstream of receptor binding, we established a high-throughput screening (HTS) platform based on pseudoviruses. We employed a three-step process to screen nearly 200,000 small molecules. First, we identified hits that inhibit pseudoviruses bearing the SARS-CoV-2 S glycoprotein. Counter-screening against pseudoviruses with the vesicular stomatitis virus glycoprotein (VSV-G), yielded sixty-five SARS-CoV-2 S-specific inhibitors. These were further tested against pseudoviruses bearing the MERS-CoV S glycoprotein, which uses a different receptor. Out of these, five compounds, which included the known broad-spectrum inhibitor Nafamostat, were subjected to further validation and tested against pseudoviruses bearing the S glycoprotein of the Alpha, Delta, and Omicron variants as well as bona fide SARS-CoV-2. This rigorous approach revealed an unreported inhibitor and its derivative as potential broad-spectrum antivirals.
Keywords: Health sciences; Pharmacology; Virology.
. 2024 May 17;27(6):110019.
doi: 10.1016/j.isci.2024.110019. eCollection 2024 Jun 21. High-throughput screening identifies broad-spectrum Coronavirus entry inhibitors
Suman Khan[SUP] 1 [/SUP], Efrat Ozer Partuk[SUP] 1 [/SUP], Jeanne Chiaravalli[SUP] 2 [/SUP], Noga Kozer[SUP] 3 [/SUP], Khriesto A Shurrush[SUP] 3 [/SUP], Yael Elbaz-Alon[SUP] 1 [/SUP], Nadav Scher[SUP] 1 [/SUP], Emilie Giraud[SUP] 2 [/SUP], Jaouen Tran-Rajau[SUP] 2 [/SUP], Fabrice Agou[SUP] 2 [/SUP], Haim Michael Barr[SUP] 3 [/SUP], Ori Avinoam[SUP] 1 [/SUP]
Affiliations
- PMID: 38883823
- PMCID: PMC11176637
- DOI: 10.1016/j.isci.2024.110019
The COVID-19 pandemic highlighted the need for antivirals against emerging coronaviruses (CoV). Inhibiting spike (S) glycoprotein-mediated viral entry is a promising strategy. To identify small molecule inhibitors that block entry downstream of receptor binding, we established a high-throughput screening (HTS) platform based on pseudoviruses. We employed a three-step process to screen nearly 200,000 small molecules. First, we identified hits that inhibit pseudoviruses bearing the SARS-CoV-2 S glycoprotein. Counter-screening against pseudoviruses with the vesicular stomatitis virus glycoprotein (VSV-G), yielded sixty-five SARS-CoV-2 S-specific inhibitors. These were further tested against pseudoviruses bearing the MERS-CoV S glycoprotein, which uses a different receptor. Out of these, five compounds, which included the known broad-spectrum inhibitor Nafamostat, were subjected to further validation and tested against pseudoviruses bearing the S glycoprotein of the Alpha, Delta, and Omicron variants as well as bona fide SARS-CoV-2. This rigorous approach revealed an unreported inhibitor and its derivative as potential broad-spectrum antivirals.
Keywords: Health sciences; Pharmacology; Virology.