Eltrombopag is a potential target for drug intervention in SARS-CoV-2 spike protein
The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a current global threat for which there is an urgent need to search for an effective therapy. The transmembrane spike (S) glycoprotein of SARS-CoV-2 directly binds to the host angiotensin-converting...
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Veröffentlicht in: | Infection, genetics and evolution genetics and evolution, 2020-11, Vol.85, p.104419-104419, Article 104419 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a current global threat for which there is an urgent need to search for an effective therapy. The transmembrane spike (S) glycoprotein of SARS-CoV-2 directly binds to the host angiotensin-converting enzyme 2 (ACE2) and mediates viral entrance, which is therefore considered as a promising drug target. Considering that new drug development is a time-consuming process, drug repositioning may facilitate rapid drug discovery dealing with sudden infectious diseases. Here, we compared the differences between the virtual structural proteins of SARS-CoV-2 and SARS-CoV, and selected a pocket mainly localizing in the fusion cores of S2 domain for drug screening. A virtual drug design algorithm screened the Food and Drug Administration-approved drug library of 1234 compounds, and 13 top scored compounds were obtained through manual screening. Through in vitro molecular interaction experiments, eltrombopag was further verified to possess a high binding affinity to S protein plus human ACE2 and could potentially affect the stability of the ACE2-S protein complex. Hence, it is worth further exploring eltrombopag as a potential drug for the treatment of SARS-CoV-2 infection.
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•Compare the differences between the structural proteins of SARS-CoV-2 and SARS-CoV.•Screen approved drugs via virtual drug design algorithm based on S2 domain pocket.•Surface plasmon resonance and Thermo Shift Assay are established for validation.•Eltrombopag showed a high binding affinity to spike protein and ACE2.•Provide a novel and rapid way to screen potent drugs during the pandemic. |
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ISSN: | 1567-1348 1567-7257 |
DOI: | 10.1016/j.meegid.2020.104419 |