Eltrombopag is a potential target for drug intervention in SARS-CoV-2 spike protein.
Infect Genet Evol
; 85: 104419, 2020 11.
Artigo
em Inglês
| 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.
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Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Benzoatos
/
Coronavírus Relacionado à Síndrome Respiratória Aguda Grave
/
Glicoproteína da Espícula de Coronavírus
/
Enzima de Conversão de Angiotensina 2
/
SARS-CoV-2
/
Hidrazinas
Tipo de estudo:
Estudo experimental
/
Estudo prognóstico
Limite:
Humanos
Idioma:
Inglês
Revista:
Infect Genet Evol
Assunto da revista:
Biologia
/
Doenças Transmissíveis
/
Genética
Ano de publicação:
2020
Tipo de documento:
Artigo
País de afiliação:
J.meegid.2020.104419
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