Lassa mammarenavirus (LASMV) is responsible for a specific type of acute viral hemorrhagic fever known as Lassa fever. Lack of effective treatments and counter-measures against the virus has resulted in a high mortality rate in its endemic regions. Therefore, in this study, a novel epitope-based vaccine has been designed using the methods of immunoinformatics targeting the glycoprotein and nucleoprotein of the virus. After numerous robust analyses, two CTL epitopes, eight HTL epitopes and seven B-cell epitopes were finally selected for constructing the vaccine. All these most promising epitopes were found to be antigenic, non-allergenic, nontoxic and non-human homolog, which made them suitable for designing the subunit vaccine. Furthermore, the selected T-cell epitopes which were found to be fully conserved across different isolates of the virus, were also considered for final vaccine construction. After that, numerous validation experiments, i.e. molecular docking, molecular dynamics simulation and immune simulation were conducted, which predicted that our designed vaccine should be stable within the biological environment and effective in combating the LASMV infection. In the end, codon adaptation and in silico cloning studies were performed to design a recombinant plasmid for producing the vaccine industrially. However, further in vitro and in vivo assessments should be done on the constructed vaccine to finally confirm its safety and efficacy. Communicated by Ramaswamy H. Sarma

RNA-binding proteins (RBPs) are integral components of cellular machinery, playing crucial roles in the regulation of gene expression and maintaining genetic stability. Their interactions with RNA molecules govern critical processes such as mRNA splicing, stability, localization, and translation, which are essential for proper cellular function. These proteins interact with RNA molecules and other proteins to form ribonucleoprotein complexes (RNPs), hence controlling the fate of target RNAs. The interaction occurs via RNA recognition motif, the zinc finger domain, the KH domain and the double stranded RNA binding motif (all known as RNA-binding domains (RBDs). These domains are found within the coding sequences (intron and exon domains), 5’ untranslated regions (5’UTR) and 3’ untranslated regions (3’UTR). Dysregulation of RBPs can lead to genomic instability, contributing to various pathologies, including cancer neurodegenerative diseases, and metabolic disorders. This study comprehensively explores the multifaceted roles of RBPs in genetic stability, highlighting their involvement in maintaining genomic integrity through modulation of RNA processing and their implications in cellular signalling pathways. Furthermore, it discusses how aberrant RBP function can precipitate genetic instability and disease progression, emphasizing the therapeutic potential of targeting RBPs in restoring cellular homeostasis. Through an analysis of current literature, this study aims to delineate the critical role of RBPs in ensuring genetic stability and their promise as targets for innovative therapeutic strategies.

Dipeptidyl peptidase-4 (DPP4) inhibitors are a potent therapeutic treatment for type 2 diabetes mellitus (T2DM). There is a family of compounds used as DPP4 inhibitors (DPP4Is) called gliptins. They bind tightly to DPP4 to form an inactive protein-ligand complex. However, there remains a need to identify novel DPP4Is that are more efficacious and safer due to the increasing prevalence of T2DM and the undesirable side effects of gliptins. To identify potential DPP4Is, we screened over 1800 novel compounds in a comparative study with gliptins. We performed dual-factor molecular docking to assess the binding affinity of the compounds to DPP4 and found four compounds with a higher binding affinity to DPP4 than currently used gliptins. The newly identified compounds interacted with the dyad glutamate (GLU205 and GLU206) and tyrosine (TYR662 and TYR666) residues in DPP4's active site. We performed molecular dynamics simulations to determine the stability of the protein-ligand complexes formed by the compounds and DPP4. Furthermore, we examined the toxicity and pharmacological profile of the compounds. The compounds are drug-like, easy to synthesize, and relatively less toxic than gliptins. Collectively, our results suggest that the novel compounds are potential DPP4Is and should be considered for further studies to develop novel antidiabetics.Communicated by Ramaswamy H. Sarma.

Background Breast cancer is one of the most common cancer types among women, especially in developing and underdeveloped nations like Nigeria. Anexelekto (AXL) is one of the well-known proteins that is implicated in various cancer types, including breast cancer, and it remains one of the focuses of targeted therapy. However, several drugs have been identified as inhibitors of this oncogenic protein, but they often come with toxic concerns in addition to their unaffordability to people of low- or middle-income countries. Thus, there is a crucial need to identify pocket-friendly inhibitors with negligible side effects targeting AXL. Therefore, bioactive compounds from plants such as Echinacea purpurea may be a promising agent in this regard. Objective The study sought to investigate the potential of bioactive compounds derived from Echinacea purpurea to inhibit the AXL protein implicated in breast cancer. Methods Structural bioinformatics via molecular docking and density functional theory (DFT) analysis was utilised for the identification of novel AXL inhibitors from Echinacea purpurea bioactive compounds. The compounds were further subjected to pharmacokinetic and drug-likeness analysis. Results obtained from the compounds were compared against those of Foretinib, a known AXL inhibitor. Additionally, their complexes with AXL were subjected to a 100 ns molecular dynamics (MD) simulation analysis utilising the Desmond v2020-4 software in Schrödinger (Academic version) in a Linux environment. Results Among all favourable binding scores, Kaempferol-7-o-Neohesperidoside, Kaempferol 3-gentiobioside-7-rhamnoside, and Kaempferol 3-o-beta-d-glucopyranosyl-7-o-alpha-L-rhamnopyranoside showed the highest binding score of -9.2, -8.9, and − 8.6 Kcal/mol, respectively, compared to Foretinib (-8.1 Kcal/mol). Stigmasterol and β-sitosterol also showed a higher binding affinity and binding score of -8.4 and − 8.3 Kcal/mol, respectively, against the AXL compared to the standard drug. DFT analysis revealed that Kaempferol 3-o-beta-d-glucopyranosyl-7-o-alpha-L-rhamnopyranoside has the highest LUMO-HOMO gap of -4.354 eV, suggesting greater potential for electron donation and high drug-enzyme reactivity. Also, the pharmacokinetic profiling of the selected compounds is favourable. Findings from MD simulation showed that the protein-ligand complexes formed by these compounds maintained structural stability, compactness, and low atomic fluctuations throughout a 100-ns simulation period. Conclusion In silico studies show that E. purpurea-derived compounds, especially Kaempferol 3-o-beta-d-glucopyranosyl-7-o-alpha-L-rhamnopyranoside, have better inhibitory potential against AXL and better pharmacokinetic profiles when compared with Foretinib. These compounds are thus proposed as novel AXL inhibitors for the treatment of breast cancer. Further, in vivo studies are needed to confirm the potency of the studied compounds.

SARS-CoV-2 (novel coronavirus responsible for coronavirus disease 2019) is a beta (β-) sub-class of the coronavirus which has caused more harm to live than expected. SARS-CoV-2 which was declared as a pandemic by the World Health Organization (WHO) on 11 March 2020, has caused governments globally to declare and implement the “lock down” policy for its citizen, including Nigeria with a large population in Africa. The country National Centre for Disease Control (NCDC) made it known the testing methods adopted by them are not effective at curtaining the large population of her citizens. Our main goal in this review is to focus on the SARS-CoV-2 pathogenesis and new diagnostic techniques approaches that can be adopted in Nigeria. A total of 88,432 testing has been carried out by the NCDC, with 14,554 confirmed cases in 200 million populations. Although the SARS-CoV-2 test adopted by the NCDC has been on the molecular testing using real-time reverse transcriptase polymerase chain reaction (RT-PCR) and antibody tests using blood, which has many demerits. We therefore recommend the NCDC should approach new diagnostic techniques like use of saliva samples and loop-mediated isothermal amplification (LAMP). Conclusively, when these methods are considered, testing rates will greatly improve.