Potential repurposing of four FDA approved compounds with antiplasmodial activity identified through proteome scale computational drug discovery and in vitro assay.

Malaria elimination can benefit from time and cost-efficient approaches for antimalarials such as drug repurposing. In this work, 796 DrugBank compounds were screened against 36 Plasmodium falciparum targets using QuickVina-W. Hits were selected after rescoring using GRaph Interaction Matching (GRIM) and ligand efficiency metrics: surface efficiency index (SEI), binding efficiency index (BEI) and lipophilic efficiency (LipE). They were further evaluated in Molecular dynamics (MD). Twenty-five protein-ligand complexes were finally retained from the 28,656 (36 × 796) dockings. Hit GRIM scores (0.58 to 0.78) showed their molecular interaction similarity to co-crystallized ligands. Minimum LipE (3), SEI (23) and BEI (7) were in at least acceptable thresholds for hits. Binding energies ranged from -6 to -11 kcal/mol. Ligands showed stability in MD simulation with good hydrogen bonding and favorable protein-ligand interactions energy (the poorest being -140.12 kcal/mol). In vitro testing showed 4 active compounds with two having IC50 values in the single-digit µM range.

SANCDB: an update on South African natural compounds and their readily available analogs.

BACKGROUND: South African Natural Compounds Database (SANCDB; https://sancdb.rubi.ru.ac.za/ ) is the sole and a fully referenced database of natural chemical compounds of South African biodiversity. It is freely available, and since its inception in 2015, the database has become an important resource to several studies. Its content has been: used as training data for machine learning models; incorporated to larger databases; and utilized in drug discovery studies for hit identifications. DESCRIPTION: Here, we report the updated version of SANCDB. The new version includes 412 additional compounds that have been reported since 2015, giving a total of 1012 compounds in the database. Further, although natural products (NPs) are an important source of unique scaffolds, they have a major drawback due to their complex structure resulting in low synthetic feasibility in the laboratory. With this in mind, SANCDB is, now, updated to provide direct links to commercially available analogs from two major chemical databases namely Mcule and MolPort. To our knowledge, this feature is not available in other NP databases. Additionally, for easier access to information by users, the database and website interface were updated. The compounds are now downloadable in many different chemical formats. CONCLUSIONS: The drug discovery process relies heavily on NPs due to their unique chemical organization. This has inspired the establishment of numerous NP chemical databases. With the emergence of newer chemoinformatic technologies, existing chemical databases require constant updates to facilitate information accessibility and integration by users. Besides increasing the NPs compound content, the updated SANCDB allows users to access the individual compounds (if available) or their analogs from commercial databases seamlessly.

Introducing and Implementing HIV Self-Testing in Côte d'Ivoire, Mali, and Senegal: What Can We Learn From ATLAS Project Activity Reports in the Context of the COVID-19 Crisis?

Background: The ATLAS program promotes and implements HIVST in Côte d'Ivoire, Mali, and Senegal. Priority groups include members of key populations-female sex workers (FSW), men having sex with men (MSM), and people who use drugs (PWUD)-and their partners and relatives. HIVST distribution activities, which began in mid-2019, were impacted in early 2020 by the COVID-19 pandemic. Methods: This article, focusing only on outreach activities among key populations, analyzes quantitative, and qualitative program data collected during implementation to examine temporal trends in HIVST distribution and their evolution in the context of the COVID-19 health crisis. Specifically, we investigated the impact on, the adaptation of and the disruption of field activities. Results: In all three countries, the pre-COVID-19 period was marked by a gradual increase in HIVST distribution. The period corresponding to the initial emergency response (March-May 2020) witnessed an important disruption of activities: a total suspension in Senegal, a significant decline in Côte d'Ivoire, and a less pronounced decrease in Mali. Secondary distribution was also negatively impacted. Peer educators showed resilience and adapted by relocating from public to private areas, reducing group sizes, moving night activities to the daytime, increasing the use of social networks, integrating hygiene measures, and promoting assisted HIVST as an alternative to conventional rapid testing. From June 2020 onward, with the routine management of the COVID-19 pandemic, a catch-up phenomenon was observed with the resumption of activities in Senegal, the opening of new distribution sites, a rebound in the number of distributed HIVST kits, a resurgence in larger group activities, and a rebound in the average number of distributed HIVST kits per primary contact. Conclusions: Although imperfect, the program data provide useful information to describe changes in the implementation of HIVST outreach activities over time. The impact of the COVID-19 pandemic on HIVST distribution among key populations was visible in the monthly activity reports. Focus groups and individual interviews allowed us to document the adaptations made by peer educators, with variations across countries and populations. These adaptations demonstrate the resilience and learning capacities of peer educators and key populations.

Oral Phyto-thymol ameliorates the stress induced IBS symptoms.

Physical stressors play a crucial role in the progression of irritable bowel syndrome (IBS). Here we report a heterogeneous physical stress induced IBS rat model which shows depression and subsequent modulation of IBS by oral treatment of thymol. Oral administration of Thymol reduces the stress induced IBS significantly altering the stress induced gastrointestinal hypermotility, prolonged the whole gut transit time, and increased abdominal withdrawal reflex suggesting gastrointestinal hypermotility and visceral discomfort caused the onset of depression. Immunohistochemical analysis in small intestine and colon of rats shows the decreased 5-HT3AR expression level while thymol treatment normalized the 5-HT3AR expression in the stressed rats. Molecular docking studies showed that thymol competes with endogenous serotonin and an antagonist, Tropisetron and all have similar binding energies to 5-HT3AR. Molecular dynamics simulations revealed that thymol and tropisetron might have similar effects on 5-HT3AR. Our study suggest that thymol improves IBS symptoms through 5-HT3AR, could be useful for the treatment of IBS.