https://www.selleckchem.com/pharmacological_epigenetics.html Older adults were more likely to be hospitalized and reported severe cases, with higher mortality rates. In addition, rural municipalities reported a higher number of COVID-19 cases and mortality related to COVID-19 per million than urban municipalities. The adjusted absolute difference in COVID-19 cases was 912.7 per million (95% Confidence Interval (CI),79.0 - 1746.4) and mortality related to COVID-19 was 390.6 per million (95% CI, 204.5 - 576.7). Urgent policy efforts are needed to mandate the use of face masks and encourage handwashing, and improve specialty care for Mexicans in rural areas. Urgent policy efforts are needed to mandate the use of face masks and encourage handwashing, and improve specialty care for Mexicans in rural areas. The development and clinical implementation of the cap-dependent endonuclease (CEN) inhibitor baloxavir marboxil was a breakthrough in influenza therapy, but it was associated with the emergence of drug-resistant variants. To design and synthesize structural analogues of CEN inhibitors and evaluate their safety, pharmacokinetics and antiviral potency in vitro and in vivo. The drug candidate AV5124 and its active metabolite AV5116 were synthesized based on pharmacophore modelling. Stability in plasma and microsomes, plasma protein binding, cytotoxicity and antiviral activities were assessed in vitro. Pharmacokinetics after IV or oral administration were analysed in CD-1 mice. Acute toxicity and protective efficacy against lethal A(H1N1)pdm09 influenza virus challenge were examined in BALB/c mice. Pharmacophore model-assisted, 3D molecular docking predicted key supramolecular interactions of the metal-binding group and bulky hydrophobic group of AV5116 with the CEN binding site (Protein Data Bank code 6FS6) that are essential for high antiviral activity. AV5116 inhibited influenza virus polymerase complexes in cell-free assays and replication of oseltamivir-susceptible a