Structural models of human ACE2 variants with SARS-CoV-2 Spike protein for structure-based drug design
Fecha
2020Autor
Sorokina, Marija
Teixeira, João M.C.
Barrera-Vilarmau, Susana
Paschke, Reinhard
Papasotiriou, Ioannis
Rodrigues, JoãoP.G. L. M.
Kastritis, Panagiotis L.
Documentos PDF
Resumen
Emergence of coronaviruses poses a threat to global health and economy. The current outbreak
of SARS-CoV-2 has infected more than 28,000,000 people and killed more than 915,000. To date,
there is no treatment for coronavirus infections, making the development of therapies to prevent
future epidemics of paramount importance. To this end, we collected information regarding
naturally-occurring variants of the Angiotensin-converting enzyme 2 (ACE2), an epithelial receptor
that both SARS-CoV and SARS-CoV-2 use to enter the host cells. We built 242 structural models of
variants of human ACE2 bound to the receptor binding domain (RBD) of the SARS-CoV-2 surface
spike glycoprotein (S protein) and refned their interfaces with HADDOCK. Our dataset includes 140
variants of human ACE2 representing missense mutations found in genome-wide studies, 39 mutants
with reported efects on the recognition of the RBD, and 63 predictions after computational alanine
scanning mutagenesis of ACE2-RBD interface residues. This dataset will help accelerate the design of
therapeutics against SARS-CoV-2, as well as contribute to prevention of possible future coronaviruses
outbreaks.
Palabras clave
Structural models; ACE2; SARS-CoV-2; Spike proteinEnlace al recurso
https://doi.org/10.1038/s41597-020-00652-6Colecciones
Estadísticas Google Analytics
Comentarios
Respuesta Comentario Repositorio Expeditio
Gracias por tomarse el tiempo para darnos su opinión.