The first description of a disease resembling dengue fever (DF) was in the 15^thcentury slave trade era by Spanish sailors visiting the Tanzania coast. The disease, then associated with evil spirits is now known to be caused by four serotypes of dengue virus (DENV1-4) that are transmitted byAedesmosquitoes. Kenya has experienced multiple outbreaks, mostly associated with DENV-2. In this study, plasma samples obtained from 37 febrile patients during a DF outbreak at Kenya’s south coast in March 2019 were screened for DENV. Total RNA was extracted and screened for the alpha- andflavi-viruses by real-time polymerase chain reaction (qPCR). DENV-3 was the only virus detected. Shotgun metagenomics and targeted sequencing were used to obtain DENV whole genomes and the complete envelope genes (E gene) respectively. Sequences were used to infer phylogenies and time-scaled genealogies. Following Maximum likelihood and Bayesian phylogenetic analysis, two DENV-3 genotypes (III, n = 15 and V, n = 2) were found. We determined that the two genotypes had been in circulation since 2015, and that both had been introduced independently. Genotype III’s origin was estimated to have been from Pakistan. Although the origin of genotype V could not be ascertained due to rarity of these sequences globally, it was most related to a 2006 Brazilian isolate. Unlike genotype III that has been described in East and West Africa multiple times, this was the second description of genotype V in Kenya. Of note, there was marked amino acid variances in the E gene between study samples and the Thailand DENV-3 strain used in the approved Dengvaxia vaccine. It remains to be seen whether these variances negatively impact the efficacy of the Dengvaxia or future vaccines.

Kigelia africana is a medicinal plant growing naturally in many parts of Africa. In Kenya, a water concoction of the plant is used to treat breast and prostate cancers. Laboratory data on its anti-cancer activity and active principles is limited, hence no scientific rationale for its medicinal use. This study reports on in-vitro toxic activities of dichloromethane and methanol extracts of the plant against human breast cancer cells and phytochemical screening of the two extracts. Plant extracts were obtained by sequential solvent extraction of dry plant material (stem bark) using analytical grade dichloromethane: methanol (1:1) and methanol (Sigma Aldrich). In-vitro anti-cancer activities of the extracts were determined using the suphorhodamine (SRB) assay against a human breast cancer cell line (HCC 1937). Preliminary Thin layer chromatography of plant extracts was done using POLYGRAM® SIL G/UV254 plates (Merck) to establish presence of different classes of secondary metabolites. In-vitro cytotoxic activities of the two extracts were significantly different (P = 0.05). The methanol extract exhibited higher activity (IC50 = 26.02 μg/ml) compared to that of dichloromethane: methanol (1:1) (IC50 = 55.01 μg/ml). Phyto-chemical screening of the two extracts revealed the presence of terpenoids, phenols, steroids and flavonoids. The high in-vitro anti-cancer activities of solvent extracts of Kigelia africana justify its use in traditional medicine to manage breast cancer. Phytochemical analysis of the extracts reveal similar profiles hence the differences in their anti-cancer activities can be attributed to quantitative variations of various classes of secondary metabolites.

Natural products (NPs) are essential in the search for new drugs to treat a wide range of diseases, including infectious and malignant disorders. However, despite the discovery of many bioactive NPs, they often do not make it to market as drugs due to toxicity and other challenges. The development of NPs into drugs is a long and expensive process, and many promising compounds are abandoned along the way. These molecules require in silico ADMET profiling in order to speed up their development into drugs lower costs, and the high attrition rate. The objective of this work was to produce thorough ADMET profiles of secondary metabolites from several classes that were isolated from Zanthoxylum species. The genus has a long history of therapeutic use, including treating tumours, hypertension, gonorrhoea, coughs, bilharzia, chest pains, and toothaches. The study used a dataset of 406 compounds from the genus for theoretical ADMET analysis. The findings revealed that 81% of the compounds met Lipinski's rule of five, indicating good oral bioavailability. The drug-likeness criteria were taken into account, with percentages ranging from 66.2 to 88.1 percent. Additionally, 9.2% of the compounds were predicted to be lead-like, demonstrating their potential as promising drug development candidates. Interestingly, none of the compounds inhibited hERG I, while 33% inhibited hERG II, potentially having cardiac implications. Additionally, 30% of the compounds exhibited AMES toxicity inhibition, while 23.6% were identified as hepatotoxic and 22.2% would cause skin sensitivity. Moreover, 81.8% of the compounds demonstrated high intestinal absorption, making them desirable for oral drugs. In conclusion, these findings highlight the diverse properties of the investigated compounds and their potential for drug development.

Cell migration plays a vital role in both health and disease. It is driven by reorganization of the actin cytoskeleton, which is regulated by actin-binding proteins cofilin and profilin. Stress-inducible phosphoprotein 1 (STIP1) is a well-described co-chaperone of the Hsp90 chaperone system, and our findings identify a potential regulatory role of STIP1 in actin dynamics. We show that STIP1 can be isolated in complex with actin and Hsp90 from HEK293T cells and directly interacts with actin in vitro via the C-terminal TPR2AB-DP2 domain of STIP1, potentially due to a region spanning two putative actin-binding motifs. We found that STIP1 could stimulate the in vitro ATPase activity of actin, suggesting a potential role in the modulation of F-actin formation. Interestingly, while STIP1 depletion in HEK293T cells had no major effect on total actin levels, it led to increased nuclear accumulation of actin, disorganization of F-actin structures, and an increase and decrease in cofilin and profilin levels, respectively. This study suggests that STIP1 regulates the cytoskeleton by interacting with actin, or via regulating the ratio of proteins known to affect actin dynamics.