Eltrombopag is a potential target for drug intervention in SARS-CoV-2 spike protein.
Infect Genet Evol
; 85: 104419, 2020 11.
Artículo
en Inglés
| 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.
Palabras clave
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Pirazoles
/
Benzoatos
/
Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo
/
Glicoproteína de la Espiga del Coronavirus
/
Enzima Convertidora de Angiotensina 2
/
SARS-CoV-2
/
Hidrazinas
Tipo de estudio:
Estudio experimental
/
Estudio pronóstico
Límite:
Humanos
Idioma:
Inglés
Revista:
Infect Genet Evol
Asunto de la revista:
Biologia
/
Enfermedades Transmisibles
/
Genética
Año:
2020
Tipo del documento:
Artículo
País de afiliación:
J.meegid.2020.104419
Similares
MEDLINE
...
LILACS
LIS