Por favor, use este identificador para citar o enlazar este ítem:
http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/1256| The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus | |
| Gordon, C Tchesnokov, E Feng, J Porter, D Gotte, M | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| Antiviral drugs for managing infections with human coronaviruses are not yet approved, posing a serious challenge to current global efforts aimed at containing the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Remdesivir (RDV) is an investigational compound with a broad spectrum of antiviral activities against RNA viruses, including SARS-CoV and Middle East respiratory syndrome (MERS-CoV). RDV is a nucleotide analog inhibitor of RNA-dependent RNA polymerases (RdRps). Here, we co-expressed the MERS-CoV nonstructural proteins nsp5, nsp7, nsp8, and nsp12 (RdRp) in insect cells as a part a polyprotein to study the mechanism of inhibition of MERS-CoV RdRp by RDV. We initially demonstrated that nsp8 and nsp12 form an active complex. The triphosphate form of the inhibitor (RDV-TP) competes with its natural counterpart ATP. Of note, the selectivity value for RDV-TP obtained here with a steady-state approach suggests that it is more efficiently incorporated than ATP and two other nucleotide analogues. Once incorporated at position i, the inhibitor caused RNA synthesis arrest at position i+3. Hence, the likely mechanism of action is delayed RNA chain termination. The additional three nucleotides may protect the inhibitor from excision by the viral 3'-5' exonuclease activity. Together, these results help to explain the high potency of RDV against RNA viruses in cell-based assays. | |
| The Journal of Biological Chemistry | |
| 2020 | |
| Preimpreso | |
| https://coronavirus.1science.com/item/0cda66afac84f24b359ce91237a0f5e770d3ce05 | |
| Inglés | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Artículos científicos |
Cargar archivos:
| Fichero | Tamaño | Formato | |
|---|---|---|---|
| 107091.pdf | 1.06 MB | Adobe PDF | Visualizar/Abrir |