Por favor, use este identificador para citar o enlazar este ítem:
http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/7549| SARS-CoV-2 comes up with a perfect recipe for disaster: Each mutation plays a specific role in the evolution of variants of concern | |
| Vaibhav Upadhyay Casey Patrick ALEXANDRA LUCAS Krishna Mallela | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| https://doi.org/10.1101/2021.12.23.474050 | |
| https://www.biorxiv.org/content/10.1101/2021.12.23.474050v1 | |
| COVID-19 pandemic has extended for close to two years with the continuous emergence of new variants. Mutations in the receptor binding domain (RBD) are of prime importance in dictating the SARS-CoV-2 spike protein function. By studying a series of single, double and triple RBD mutants, we have delineated the individual and collective effects of RBD mutations in a variant of concern (VOC) containing multiple mutations (Gamma variant; K417T/E484K/N501Y) on binding to angiotensin converting enzyme 2 (ACE2) receptor, antibody escape and protein stability. Our results show that each mutation in the VOC serves a distinct function that improves virus fitness landscape supporting its positive selection, even though individual mutations have deleterious effects that make them prone to negative selection. K417T contributes to increased expression, increased stability and escape from class 1 antibodies; however, it has decreased ACE2 binding. E484K contributes to escape from class 2 antibodies; however, it has decreased expression, decreased stability, and decreased ACE2 binding affinity. N501Y increases receptor binding affinity; however, it has decreased stability and decreased expression. But when these mutations come together, the deleterious effects are mitigated in the triple mutant due to the presence of compensatory effects, which improves the chances of selection of mutations together. These results show the implications of presence of multiple mutations on virus evolution and indicate the emergence of future SARS-CoV-2 variants with multiple mutations that enhance viral fitness on different fronts by balancing both positive and negative selection. | |
| medRxiv and bioRxiv | |
| 25-12-2021 | |
| Preimpreso | |
| www.biorxiv.org | |
| Inglés | |
| Epidemia COVID-19 | |
| Público en general | |
| VIRUS RESPIRATORIOS | |
| Versión publicada | |
| publishedVersion - Versión publicada | |
| Aparece en las colecciones: | Artículos científicos |
Cargar archivos:
| Fichero | Tamaño | Formato | |
|---|---|---|---|
| SARS COV2 comes up with a perfect recipe for disaster_ Each mutation plays a specific role in the evolution of variants of concern.pdf | 1.65 MB | Adobe PDF | Visualizar/Abrir |