Exploration of phytochemical compounds against Marburg virus using QSAR, molecular dynamics, and free energy landscape.

Marburg virus disease (MVD) is caused by the Marburg virus, a one-of-a-kind zoonotic RNA virus from the genus Filovirus. Thus, this current study employed AI-based QSAR and molecular docking-based virtual screening for identifying potential binders against the target protein (nucleoprotein (NP)) of the Marburg virus. A total of 2727 phytochemicals were used for screening, out of which the top three compounds (74977521, 90470472, and 11953909) were identified based on their predicted bioactivity (pIC50) and binding score (< - 7.4 kcal/mol). Later, MD simulation in triplicates and trajectory analysis were performed which showed that 11953909 and 74977521 had the most stable and consistent complex formations and had the most significant interactions with the highest number of hydrogen bonds. PCA (principal component analysis) and FEL (free energy landscape) analysis indicated that these compounds had favourable energy states for most of the conformations. The total binding free energy of the compounds using the MM/GBSA technique showed that 11953909 (ΔGTOTAL = - 30.78 kcal/mol) and 74977521 (ΔGTOTAL = - 30 kcal/mol) had the highest binding affinity with the protein. Overall, this in silico pipeline proposed that the phytochemicals 11953909 and 74977521 could be the possible binders of NP. This study aimed to find phytochemicals inhibiting the protein's function and potentially treating MVD.

Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture.

The human malaria parasite Plasmodium falciparum is responsible for the majority of mortality and morbidity caused by malaria infection and differs from other human malaria species in the degree of accumulation of parasite-infected red blood cells in the microvasculature, known as cytoadherence or sequestration. In P. falciparum, cytoadherence is mediated by a protein called PfEMP1 which, due to its exposure to the host immune system, undergoes antigenic variation resulting in the expression of different PfEMP1 variants on the infected erythrocyte membrane. These PfEMP1s contain various combinations of adhesive domains, which allow for the differential engagement of a repertoire of endothelial receptors on the host microvasculature, with specific receptor usage associated with severe disease. We used a co-culture model of cytoadherence incubating human brain microvascular endothelial cells with erythrocytes infected with two parasite lines expressing different PfEMP1s that demonstrate different binding profiles to vascular endothelium. We determined the transcriptional profile of human brain microvascular endothelial cells (HBMEC) following different incubation periods with infected erythrocytes, identifying different transcriptional profiles of pathways previously found to be involved in the pathology of severe malaria, such as inflammation, apoptosis and barrier integrity, induced by the two PfEMP1 variants.

Elevated Levels of Procoagulant Microvesicles and Tissue-Factor Bearing Microvesicles in Malaria Patients.

Background: Procoagulant microvesicles (MVs) are submicron membrane fragments released from activated cells and cells undergoing apoptosis. The procoagulant activity of MVs is enhanced in the presence of tissue factor (TF). MVs and TF are active mediators that induce pro-inflammatory response and prothrombotic tendency and have been linked to the severity of several disorders, including malaria infection. The current study aimed to measure the levels of circulating procoagulant MVs and TF-bearing MVs in malaria patients and correlate these levels with other hematological parameters and parasitemia. Materials and Methods: Levels of MVs and TF-bearing MVs in the plasma of children and adult patients infected with Plasmodium falciparum were measured alongside matched healthy controls. Results: Patients with Plasmodium falciparum infection had ~3.8 times MVs (p < 0.0001) and ~13.0 times TF-bearing MVs compared to the matched healthy controls. MVs showed inverse significant correlation with platelet count (p = 0.0055), hemoglobin (p = 0.0004) and parasitemia. Conclusion: Elevated levels of MVs and TF-bearing MVs could be useful biomarkers to evaluate the procoagulant activity, inflammatory response and parasitemia levels in malaria infection, aiding in better management of the disease.

An Insight into Advances in Developing Nanotechnology Based Therapeutics, Drug Delivery, Diagnostics and Vaccines: Multidimensional Applications in Tuberculosis Disease Management.

Tuberculosis (TB), one of the deadliest contagious diseases, is a major concern worldwide. Long-term treatment, a high pill burden, limited compliance, and strict administration schedules are all variables that contribute to the development of MDR and XDR tuberculosis patients. The rise of multidrug-resistant strains and a scarcity of anti-TB medications pose a threat to TB control in the future. As a result, a strong and effective system is required to overcome technological limitations and improve the efficacy of therapeutic medications, which is still a huge problem for pharmacological technology. Nanotechnology offers an interesting opportunity for accurate identification of mycobacterial strains and improved medication treatment possibilities for tuberculosis. Nano medicine in tuberculosis is an emerging research field that provides the possibility of efficient medication delivery using nanoparticles and a decrease in drug dosages and adverse effects to boost patient compliance with therapy and recovery. Due to their fascinating characteristics, this strategy is useful in overcoming the abnormalities associated with traditional therapy and leads to some optimization of the therapeutic impact. It also decreases the dosing frequency and eliminates the problem of low compliance. To develop modern diagnosis techniques, upgraded treatment, and possible prevention of tuberculosis, the nanoparticle-based tests have demonstrated considerable advances. The literature search was conducted using Scopus, PubMed, Google Scholar, and Elsevier databases only. This article examines the possibility of employing nanotechnology for TB diagnosis, nanotechnology-based medicine delivery systems, and prevention for the successful elimination of TB illnesses.

A Cross-Sectional Study on the Knowledge of Sexually Transmitted Diseases among Young Adults Living in Albaha, Saudi Arabia.

BACKGROUND: Sexually transmitted diseases (STDs) remain one of the most important health challenges in not only developing countries but also developed countries. Discussing STDs in the Saudi society is considered taboo, as social factors and ethics give rise to many obstacles. This study evaluates the knowledge of STDs among young adult students enrolled in Albaha University. METHODS: This research is a cross-sectional study involving 1902 young adult students registered at Albaha University. STDs knowledge scores (STDs-KSs) were calculated using a predesigned and validated STDs knowledge questionnaire with 27 items adapted from previously developed questionnaires. RESULTS: The estimated overall mean of STDs-KS was 7.95 ± 4.29. Female participants showed a significantly higher mean of STDs-KS, compared to males (8.51 ± 4.14 vs. 7.32 ± 4.38, p < 0.0001). Participants registered in health sciences programs showed higher STDs-KS, compared to participants from arts and sciences programs (p < 0.0001). CONCLUSIONS: Evidence from this study suggests a lack of STDs knowledge among young adults. To promote STDs awareness among this population, more health educational programs should be included in school curricula at the late stages of secondary education.