Eltrombopag is a potential target for drug intervention in SARS-CoV-2 spike protein.
Infect Genet Evol
; 85: 104419, 2020 11.
Article
in English
| MEDLINE | ID: covidwho-997272
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
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pyrazoles
/
Benzoates
/
Severe acute respiratory syndrome-related coronavirus
/
Spike Glycoprotein, Coronavirus
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
/
Hydrazines
Type of study:
Experimental Studies
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
Infect Genet Evol
Journal subject:
Biology
/
Communicable Diseases
/
Genetics
Year:
2020
Document Type:
Article
Affiliation country:
J.meegid.2020.104419
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