Details

Autor(en) / Beteiligte

• Feng, Siqin
• Luan, Xiaodong
• Wang, Yifei
• Wang, Hui
• Zhang, Zhiyu
• Wang, Yiyang
• Tian, Zhuang
• Liu, Meixi
• Xiao, Ying
• Zhao, Yong
• Zhou, Ruilin
• Zhang, Shuyang

Titel

Eltrombopag is a potential target for drug intervention in SARS-CoV-2 spike protein

Ist Teil von

• Infection, genetics and evolution, 2020-11, Vol.85, p.104419-104419, Article 104419

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •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.