MATERIALS AND METHODS: In this study, we employed in silico methods to assess the inhibitory activity of natural products from traditional Chinese medicine (TCM) against four EBOV proteins that are crucial for viral replication and assembly: VP40, VP35, VP30, and VP24. We performed molecular docking of TCM compounds with the EBOV proteins and screened them based on their docking scores, binding free energies, and pharmacokinetic properties.
RESULTS: Our results pinpointed eight TCM compounds (TCM1797, TCM2872, TCM250, TCM2837, TCM2644, TCM4697, TCM2322, and TCM277) that exhibited superior efficacy in inhibiting all the EBOV proteins compared to the controls. These compounds interacted with key residues of the EBOV proteins through various types of bonds, such as hydrogen bonds, salt bridges, and π-π interactions, forming stable complexes that could disrupt the function of the EBOV proteins. These compounds were found to possess known antiviral activity, acceptable pharmacokinetic properties, and human usage history, which make them promising candidates for anti-EBOV drug development. Moreover, the molecular simulation analysis confirmed the binding stability, structural compactness, and residue flexibility properties of these compounds. Furthermore, the binding free energy results revealed that VP30-TCM2644, VP30-TCM4697, VP35-TCM2837, VP24-TCM250, and VP24-TCM277 complexes exhibit significant binding free energy values compared to the control ligands. Principal Component Analysis (PCA) and Free Energy Landscape (FEL) results revealed the trajectories' motion and conformational energy states.
CONCLUSIONS: Our findings provide valuable insights into the molecular mechanisms driving the efficacy of TCM drugs against EBOV and suggest novel approaches for the development of anti-EBOV therapies.
OBJECTIVE: This study aimed to assess the general population's knowledge, symptom experiences, and willingness to vaccinate against IPIs across six countries: Malaysia, Vietnam, India, Pakistan, and China.
MATERIALS AND METHODS: A cross-sectional online survey was conducted between June and December 2023 across six countries in Asia region. Participants completed a self-administered online questionnaire that assessed demographic information, knowledge of IPIs, symptom experiences, and willingness to receive a vaccine against IPIs for themselves and their children. Univariate and multivariable logistic analyses were performed to determine the factors related to vaccination the willingness.
RESULTS: A total of 5470 complete responses were received. The highest proportion of individuals willing to receive the vaccine was in India (86.1 %), followed by China (80.8 %) and Pakistan (75 %), with Vietnam having the lowest proportion at 50.1 %. For child vaccination, China had the highest willingness (83.3 %). A higher knowledge score was significantly associated with increased willingness to be vaccinated [adjusted odds ratio (aOR)= 1.91, 95 % CI: 1.70-2.15]. Additionally, a higher symptom experience score was significantly associated with greater vaccination willingness (aOR=1.71, 95 % CI: 1.50-1.94). Females residing in urban-suburban areas showed significantly higher vaccination intentions. The willingness to vaccinate children against IPIs closely mirrored the trends observed in self-vaccination willingness, with knowledge being the only factor significantly associated with the willingness to vaccinate children.
CONCLUSION: The study underscores the importance of enhancing educational efforts regarding neglected IPIs and vaccination, particularly when vaccines are available and recommended.
METHODS: In this study we used the docking, molecular dynamics simulation and binding free energy approaches to identify the potent inhibitor of NLRP3 by screening the African phytocompounds and traditional Chinese medicine databases.
RESULTS: Our virtual drug screening analysis identified two lead compounds from each database, characterized by high docking scores such as SA-21676268 (-8.135 kcal/mol), SA-167673 (-10.251 kcal/mol), EA-45360194 (-10.376 kcal/mol), EA-46881231 (-10.011 kcal/mol), NEA-44258150 (-9.856 kcal/mol), NEA-135926572 (-7.662 kcal/mol), NA-163089376 (-9.237 kcal/mol), NA-440735 (-8.826 kcal/mol), TCM-392442 (-10.438 kcal/mol), and TCM-10043097 (-9.046 kcal/mol) which highlighted the strong binding affinity as compared to the control NP3-146 drug (-5.09 kcal/mol). Moreover, the values of dissociation constant further validated the strong binding affinity between the identified lead compounds and NLRP3. The dynamic stability and strong bonding energies of the lead compounds-NLRP3 complexes were confirmed by the molecular dynamic simulation and binding free energy calculation. The analysis of ADMET properties for all compounds indicated high intestinal absorption, water solubility, absence of hepatotoxicity, and skin sensitivity.
CONCLUSION: In conclusion, our molecular simulations and binding free energy calculations confirmed the strong affinity of these lead compounds for NLRP3 as compared to the control drug, highlighting their potential as part of a combinatorial therapeutic strategy for HS to effectively reduce disease-related inflammation.