Structural and Dynamical Basis of VP35-RBD Inhibition by Marine Fungi Compounds to Combat Marburg Virus Infection.

The Marburg virus (MBV), a deadly pathogen, poses a serious threat to world health due to the lack of effective treatments, calling for an immediate search for targeted and efficient treatments. In this study, we focused on compounds originating from marine fungi in order to identify possible inhibitory compounds against the Marburg virus (MBV) VP35-RNA binding domain (VP35-RBD) using a computational approach. We started with a virtual screening procedure using the Lipinski filter as a guide. Based on their docking scores, 42 potential candidates were found. Four of these compounds-CMNPD17596, CMNPD22144, CMNPD25994, and CMNPD17598-as well as myricetin, the control compound, were chosen for re-docking analysis. Re-docking revealed that these particular compounds had a higher affinity for MBV VP35-RBD in comparison to the control. Analyzing the chemical interactions revealed unique binding properties for every compound, identified by a range of Pi-cation interactions and hydrogen bond types. We were able to learn more about the dynamic behaviors and stability of the protein-ligand complexes through a 200-nanosecond molecular dynamics simulation, as demonstrated by the compounds' consistent RMSD and RMSF values. The multidimensional nature of the data was clarified by the application of principal component analysis, which suggested stable conformations in the complexes with little modification. Further insight into the energy profiles and stability states of these complexes was also obtained by an examination of the free energy landscape. Our findings underscore the effectiveness of computational strategies in identifying and analyzing potential inhibitors for MBV VP35-RBD, offering promising paths for further experimental investigations and possible therapeutic development against the MBV.

The Relationship Between Menstrual Cycle Irregularities and COVID-19 Vaccination.

Background After COVID-19 vaccination, females reported irregularities and changes in their menstrual cycle. We aimed to explore the menstrual irregularities following COVID-19 vaccination in Saudi women of childbearing age. Methodology The study was a cross-sectional study conducted among women in Riyadh, Saudi Arabia, who had no history of menstrual irregularities before receiving the first dose of the COVID-19 vaccine. The participants filled out an online self-administered questionnaire via Google Form about any menstrual irregularities they experienced after receiving the COVID-19 vaccine. Results A total of 535 participants completed the survey. The study found that 41.7% (223) of women experienced menstrual changes after the first dose of the COVID-19 vaccine, increasing to 44.1% (236) after the second dose. The incidence of these changes varied between the first and second doses. For example, the incidence of changes in period duration decreased from 51.6% to 48.3% after the first and second doses, respectively. Similarly, the incidence of delayed periods decreased from 48.4% to 47.9%, while dysmenorrhea increased slightly from 30.9% to 32.2% after the two doses. The incidence of heavier menstrual flow increased from 26.9% to 30.5%, while the incidence of lighter menstrual flow decreased from 26.9% to 24.6% after the first and second doses, respectively. Conclusions There is an increased incidence of changes in menstrual cycle after COVID-19 vaccination, particularly in menstrual cycle length, menstrual pain, and the flow of menstruation. Future studies are needed to investigate the potential underlying biological mechanisms.