Multi-target molecular dynamic simulations reveal glutathione-S-transferase as the most favorable drug target of knipholone in Plasmodium falciparum.

Knipholone is an antiplasmodial phytocompound obtained from the roots of Kniphofia foliosa. Despite several available studies, the molecular drug targets of knipholone in P. falciparum remained unknown. Nowadays, in silico techniques are widely used to study the molecular interactions between compounds and proteins as they provide results quickly with high precision and accuracy. In this study, we aim to identify the potential molecular drug targets of knipholone in P. falciparum. We selected 10 proteins of P. falciparum with unique metabolic functions and we found that knipholone showed better binding affinity than the native ligands of 6 proteins. Out of the 6 proteins, knipholone showed better enzyme inhibitory potential than the native ligands of 4 proteins. We carried out a 100 ns MD simulations for knipholone and the native ligands of four proteins and this was followed by binding free energy calculations. In each step, the performance of knipholone was compared to the native ligands of the proteins. Knipholone outperformed the native ligand of Glutathione-S-Transferase (1OKT) at crucial computational studies as evidence from the lower protein-ligand root mean square deviation value, protein root mean square fluctuation value, and protein-ligand binding free energies. The ligand properties of knipholone provide additional evidence for its stability and it maintains adequate protein-ligand contacts during the entire simulation. The density functional theory study also supported the stability of knipholone at the active binding site of 1OKT. From the studied proteins, we conclude that Glutathione-S-Transferase is the most favorable drug target for knipholone in P. falciparum.Communicated by Ramaswamy H. Sarma.

CPMPARISON between COVID-19 and MERS demographic data in Saudi Arabia: a retrospective study.

The outbreak of corona virus disease (COVID-19) caused by the new severe acute respiratory syndrome corona virus 2 began in Wuhan, China, resulting in respiratory disorders. In January of 2020, the World Health Organization declared the outbreak a pandemic owing to its global spread. Because no studies have investigated COVID-19 in Saudi Arabia, this study investigated similarities and differences between demographic data during the COVID-19 and Middle East respiratory syndrome (MERS) outbreaks in Saudi Arabia. A retrospective trend analysis was performed to assess demographic data of all laboratory-confirmed MERS and COVID-19 cases. Patients' charts were reviewed for data on demographics, mortality, citizenship, sex ratio, and age groups with descriptive and comparative statistics; the data were analyzed using a non-parametric binomial test and chi-square test. Of all COVID-19 patients in Saudi Arabia,78%were male patients and 22% were female patients. This proportion of male COVID-19 patients was similar to that of male MERS patients, which also affected male patients more frequently than female patients. The number of COVID-19-positive Saudi cases was lower than that of non-Saudi cases, which were in contrast to that of MERS; COVID-19 appeared to be remarkably similar to MERS with respect to recovered cases. However, the numbers of critical and dead COVID-19 patients have been much lower than those of MERS patients. The largest proportion of COVID-19 and MERS cases (44.05% and 40.8%, respectively) were recorded in the Western region. MERS and COVID-19 exhibited similar threats to the lives of adults and the elderly, despite lower mortality rates during the COVID-19 epidemic. Targeted prevention of and interventions against MERS should be allocated populations according to the areas where they inhabit. However, much more information regarding the dynamics and epidemiology of COVID-19 in Saudi Arabia is needed.Abbrevation : MERS: Middle East Respiratory syndrome; COVID-19: Corona Virus Disease 2019.