tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Xiaodong Luan[SUP] 2 [/SUP], Yifei Wang[SUP] 3 [/SUP], Hui Wang[SUP] 4 [/SUP], Zhiyu Zhang[SUP] 4 [/SUP], Yiyang Wang[SUP] 3 [/SUP], Zhuang Tian[SUP] 4 [/SUP], Meixi Liu[SUP] 4 [/SUP], Ying Xiao[SUP] 4 [/SUP], Yong Zhao[SUP] 5 [/SUP], Ruilin Zhou[SUP] 4 [/SUP], Shuyang Zhang[SUP] 6 [/SUP]
Affiliations
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.
. 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[SUP] 1 [/SUP], Xiaodong Luan[SUP] 2 [/SUP], Yifei Wang[SUP] 3 [/SUP], Hui Wang[SUP] 4 [/SUP], Zhiyu Zhang[SUP] 4 [/SUP], Yiyang Wang[SUP] 3 [/SUP], Zhuang Tian[SUP] 4 [/SUP], Meixi Liu[SUP] 4 [/SUP], Ying Xiao[SUP] 4 [/SUP], Yong Zhao[SUP] 5 [/SUP], Ruilin Zhou[SUP] 4 [/SUP], Shuyang Zhang[SUP] 6 [/SUP]
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.