In silico investigation of potential small molecule inhibitors of the SARS-CoV-2 nsp10-nsp16 methyltransferase complex

The COVID-19 pandemic caused by SARS-CoV-2 has resulted in an international health emergency. The SARS-CoV-2 nsp16 is an S-adenosyl-L-methionine (SAM)-dependent methyltransferase, and with its cofactor nsp10, is responsible for RNA cap formation. This study aimed to identify small molecules binding...

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Detalles Bibliográficos
Autores principales: Liang, Julia, Pitsillou, Eleni, Burbury, Lucy, Hung, Andrew, Karagiannis, Tom C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2021
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032478/
https://www.ncbi.nlm.nih.gov/pubmed/33850334
http://dx.doi.org/10.1016/j.cplett.2021.138618
Descripción
Sumario:The COVID-19 pandemic caused by SARS-CoV-2 has resulted in an international health emergency. The SARS-CoV-2 nsp16 is an S-adenosyl-L-methionine (SAM)-dependent methyltransferase, and with its cofactor nsp10, is responsible for RNA cap formation. This study aimed to identify small molecules binding to the SAM-binding site of the nsp10-nsp16 heterodimer for potential inhibition of methyltransferase activity. By screening a library of 300 compounds, 30 compounds were selected based on binding scores, side-effects, and availability. Following more advanced docking, six potential lead compounds were further investigated using molecular dynamics simulations. This revealed the dietary compound oleuropein as a potential methyltransferase inhibitor.

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