Deep Learning and Structure-Based Virtual Screening for Drug Discovery against NEK7: A Novel Target for the Treatment of Cancer.

NIMA-related kinase7 (NEK7) plays a multifunctional role in cell division and NLRP3 inflammasone activation. A typical expression or any mutation in the genetic makeup of NEK7 leads to the development of cancer malignancies and fatal inflammatory disease, i.e., breast cancer, non-small cell lung cancer, gout, rheumatoid arthritis, and liver cirrhosis. Therefore, NEK7 is a promising target for drug development against various cancer malignancies. The combination of drug repurposing and structure-based virtual screening of large libraries of compounds has dramatically improved the development of anticancer drugs. The current study focused on the virtual screening of 1200 benzene sulphonamide derivatives retrieved from the PubChem database by selecting and docking validation of the crystal structure of NEK7 protein (PDB ID: 2WQN). The compounds library was subjected to virtual screening using Auto Dock Vina. The binding energies of screened compounds were compared to standard Dabrafenib. In particular, compound 762 exhibited excellent binding energy of -42.67 kJ/mol, better than Dabrafenib (-33.89 kJ/mol). Selected drug candidates showed a reactive profile that was comparable to standard Dabrafenib. To characterize the stability of protein-ligand complexes, molecular dynamic simulations were performed, providing insight into the molecular interactions. The NEK7-Dabrafenib complex showed stability throughout the simulated trajectory. In addition, binding affinities, pIC50, and ADMET profiles of drug candidates were predicted using deep learning models. Deep learning models predicted the binding affinity of compound 762 best among all derivatives, which supports the findings of virtual screening. These findings suggest that top hits can serve as potential inhibitors of NEK7. Moreover, it is recommended to explore the inhibitory potential of identified hits compounds through in-vitro and in-vivo approaches.

Microbiome profile of South Korean vector mosquitoes.

This research offers a comprehensive exploration of the microbial communities associated with vector mosquitoes from South Korea. Aedes albopictus, Anopheles sinensis, and Culex molestus are vectors of pathogens, and understanding the intricacies of their microbiome profile is paramount for unraveling their roles in disease transmission dynamics. In this study, we characterized the microbiome of the midguts of adult female vector mosquitoes collected from different locations in South Korea. After DNA extraction from dissected mosquito midguts, we used the Illumina MiSeq next-generation sequencing to obtain sequences spanning the V4 hypervariable region of the bacteria 16S rRNA. Morphological and molecular characterization using 506-bp mitochondrial 16S rRNA was used to identify the mosquito species before amplicon sequencing. Across the three vector mosquitoes surveyed, 21 bacteria genera belonging to 20 families and 5 phyla were discovered. Proteobacteria and Bacteriodota were the major phyla of bacteria associated with the three mosquito species. There were significant differences in the gut microbiome genera composition between the species and little variation in the gut microbiome between individuals of the same mosquito species. Wolbachia is the most dominant genus in Aedes while Aeromonas, Acinetobacter, and unassigned taxa are the most common in An. sinensis. In addition to that, Chromobacterium, Chryseobacterium, and Aeromonas are dominant in Cx. molestus. This study sheds light on the complex interactions between mosquitoes and their microbiome, revealing potential implications for vector competence, disease transmission, and vector control strategies.

Complete mitochondrial genome of a malaria vector mosquito Anopheles sinensis from South Korea.

We present the complete mitochondrial genome of a Malaria vector Mosquito Anopheles sinensis Wiedemann, 1828 from South Korea. The mitochondrial genome is about 15,421 bp long and contains 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and an A-T rich region. The present data were compared with those from China with respect to PCG sequence differences, tRNA structure, gene order, and control region (CR) structure. An. sinensis mitochondrial genomes from northeast Asia share identical gene composition and gene order. In contrast, they have distinct differences in the CR within the range 8.75% (51/583 bp) to 9.95% (58/583 bp). The phylogenetic analysis showed that An. sinensis from South Korea was clustered together with those from China, but there existed distinct genetic distance between the two. Likewise, mitochondrial genome sequences from other Anopheles species were employed to infer phylogenetic relationships among the members of the genus Anopheles. This study further promotes the enrichment of An. sinensis mitochondrial genome data, providing useful information for their mitochondrial genetic differences along with geographical distances in northeast Asia.

Larvicidal Activity of Methyl Benzoate, a Volatile Organic Compound, Against the Mosquitoes Aedes albopictus and Culex pipiens (Diptera: Culicidae).

Methyl benzoate (MBe) is a volatile organic molecule found in various plants; it is used as an insect semiochemical. MBe also has a biorational insecticidal effect against various agricultural and urban arthropod pests. The present study was the first to assess the larvicidal potential of MBe against fourth-instar larvae of the mosquitoes Aedes albopictus (Skuse) and Culex pipiens (L.). A positive association was observed between MBe concentrations and larval mortality in both the species. The highest mortality recorded was 100% for Ae. albopictus and 56% for Cx. pipiens after 24 h of exposure to 200 ppm MBe. The lethal median concentration (LC50) values of MBe against fourth-instar larvae of Ae. albopictus and Cx. pipiens were 61 ppm and 185 ppm, respectively. These results suggest that MBe has great potential for use as an environmentally friendly larvicidal agent for mosquito control.

Malaria vaccine: The lasting solution to malaria burden in Africa.

Malaria is one of the deadliest infectious diseases in Africa. Many measures have been taken over the past few years to reduce the burden of malaria on public health following the recommendation of WHO, still, malaria has continued to rake devastation in Africa. Combating malaria in Africa has grown into an international concern. The eradication of malaia is a long-standing goal of public health initiatives globally. The development of vaccines will go a long way to provide the required immunity needed for the people living with malaria or vulnerable to malaria. It is imperative that a vaccine should be produced and rolled out for use, especially during the time of the COVID-19 pandemic when attention is given to mitigating the impact of the pandemic on public health. The malaria vaccine will reduce the number of hospital admission for malaria illness among children and other age groups. Africa will need to build strong innovations to overcome country-specific challenges in vaccination drive, human resources, and supply chain management. Accelerating education, sensitization, diagnosis, and eradication through joint efforts of the government, healthcare professionals and general population will help to prevent the dual synchronous epidemic of COVID-19 and Malaria in Africa.

Genetic Relationship of Fall Armyworm (Spodoptera frugiperda) Populations That Invaded Africa and Asia.

The fall armyworm, Spodoptera frugiperda, is an important agricultural pest native to tropical and subtropical regions of the Western Hemisphere, and has invaded Africa and further spread into most countries of Asia within two years. Here, we analyzed the genetic variation of invaded populations by comparing the nucleotide sequences of two genes: the nuclear Z-chromosome linked gene triose phosphate isomerase (Tpi) and the mitochondrial gene cytochrome oxidase subunit I (COI) of 27 specimens collected in Africa (DR Congo, Tanzania, Uganda, and Zimbabwe) and Asia (Bangladesh, Korea, Nepal, and Vietnam). The results revealed that 25 specimens were from a heterogeneous hybrid (Tpi-corn strain and COI-rice strain; Tpi-C/COI-R) of the corn strain male and rice strain female, but two specimens were from a homogenous corn strain (Tpi-corn strain and COI-corn strain; Tpi-C/COI-C). The further analysis of the fourth exon and the fourth intron sequences of the Tpi gene identified at least four subgroups of the corn strain. These four genetic subgroups were identified in Africa and Asia, suggesting no significant genetic change due to the rapid migration within two years. Our study provides essential information for understanding the genetic diversity of fall armyworm in new habitats.