ABSTRACT
The pandemic became a great challenge for many aspects of life, economic performance is no ex-ception. There is evidence that the Employed Economically Active Population (EAP) decreased in Mex-ico as an effect of Covid-19, however, the behavior of the income of the Economically Active Population (EAP) that remained employed is unknown. In this context, the objective of this research is to analyze the behavior of the EAP income for each sector of activity in Mexico in times of pandemic (2020 and 1 quarter of 2021). As a methodology, the Mincer wage model was used and the rate of revenue growth was observed. The data were obtained from the National Survey of Occupation and Employment (NSOE). The results show that the EAP that works in the sectors of "Agriculture, livestock, forestry, fishing and hunting" and "Mining", suffered the greatest decrease in their income. Finally, it is concluded that Covid-19 caused the decrease in the EAP in Mexico, but also the decrease in the income of those people who have kept their jobs. © 2022, Revista Portuguesa de Estudos Regionais. All rights reserved.
ABSTRACT
Remdesivir (RDV) prodrug can be metabolized into a triphosphate form nucleotide analogue (RDV-TP) to bind and insert into the active site of viral RNA dependent RNA polymerase (RdRp) to further interfere with viral genome replication. In this work, we computationally studied how RDV-TP binds and inserts to the SARS-CoV-2 RdRp active site, in comparison with natural nucleotide substrate adenosine triphosphate (ATP). To do that, we first constructed atomic structural models of an initial binding complex (active site open) and a substrate insertion complex (active site closed), based on high-resolution cryo-EM structures determined recently for SARS-CoV-2 RdRp or non-structural protein (nsp) 12, in complex with accessory protein factors nsp7 and nsp8. By conducting all-atom molecular dynamics simulation with umbrella sampling strategies on the nucleotide insertion between the open and closed state RdRp complexes, our studies show that RDV-TP can initially bind in a comparatively stabilized state to the viral RdRp active site, as it primarily forms base stacking with the template uracil nucleotide (nt +1), which under freely fluctuations supports a low free energy barrier of the RDV-TP insertion (similar to 1.5 kcal mol(-1)). In comparison, the corresponding natural substrate ATP binds initially to the RdRp active site in Watson-Crick base pairing with the template nt, and inserts into the active site with a medium low free energy barrier (similar to 2.6 kcal mol(-1)), when the fluctuations of the template nt are well quenched. The simulations also show that the initial base stacking of RDV-TP with the template can be specifically stabilized by motif C-S759, S682 (near motif B) with the base, and motif G-K500 with the template backbone. Although the RDV-TP insertion can be hindered by motif F-R555/R553 interaction with the triphosphate, the ATP insertion seems to be facilitated by such interactions. The inserted RDV-TP and ATP can be further distinguished by specific sugar interaction with motif B-T687 and motif A-D623, respectively.