Infect Genet Evol . Eltrombopag Is a Potential Target for Drug Intervention in SARS-CoV-2 Spike Protein

[tetano]

Infect Genet Evol


. 2020 Jun 12;104419.
doi: 10.1016/j.meegid.2020.104419. Online ahead of print.
Eltrombopag Is a Potential Target for Drug Intervention in SARS-CoV-2 Spike Protein


Siqin Feng ¹ , Xiaodong Luan ² , Yifei Wang ³ , Hui Wang ⁴ , Zhiyu Zhang ⁴ , Yiyang Wang ³ , Zhuang Tian ⁴ , Meixi Liu ⁴ , Ying Xiao ⁴ , Yong Zhao ⁵ , Ruilin Zhou ⁴ , Shuyang Zhang ⁶



Affiliations

• PMID: 32540428
• DOI: 10.1016/j.meegid.2020.104419

Abstract

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.

Keywords: Homology Modeling; SARS-CoV-2; Surface plasmon resonance; Virtual drug design.