Drug Repurposing of Itraconazole and Estradiol Benzoate against COVID‐19 by Blocking SARS‐CoV‐2 Spike Protein‐Mediated Membrane Fusion. Issue 5 (22nd February 2021) - Yang, Chan
Abstract: SARS‐CoV‐2 caused the emerging epidemic of coronavirus disease in 2019 (COVID‐19). To date, there are more than 82.9 million confirmed cases worldwide, there is no clinically effective drug against SARS‐CoV‐2 infection. The conserved properties of the membrane fusion domain of the spike (S) protein across SARS‐CoV‐2 make it a promising target to develop pan‐CoV therapeutics. Herein, two clinically approved drugs, Itraconazole (ITZ) and Estradiol benzoate (EB), are found to inhibit viral entry by targeting the six‐helix (6‐HB) fusion core of SARS‐CoV‐2 S protein. Further studies shed light on the mechanism that ITZ and EB can interact with the heptad repeat 1 (HR1) region of the spike protein, to present anti‐SARS‐CoV‐2 infections in vitro, indicating they are novel potential therapeutic remedies for COVID‐19 treatment. Furthermore, ITZ shows broad‐spectrum activity targeting 6‐HB in the S2 subunit of SARS‐CoV and MERS‐CoV S protein, inspiring that ITZ have the potential for development as a pan‐coronavirus fusion inhibitor. Abstract : An effective drug against COVID‐19 is urgently needed while the current SARS‐CoV‐2 pandemic. Here Itraconazole and Estradiol benzoate are identified to inhibit SARS‐CoV‐2 infection via blocking the spike protein S2 subunit‐mediated membrane fusion and entry into the host cell by targeting the highly conserved six‐helical bundle (6‐HB) fusion core. Furthermore, Itraconazole is confirmed as a potential broad‐spectrum coronavirus fusion inhibitor.