Dichlorvos (DDVP) has been abused in Nigeria for suicide attempts, topical applications to treat an ectoparasitic infestation, and indiscriminate use on farm produce. Exposure to this compound in subacute concentration can cause toxicity in different tissues by alteration of the cellular antioxidative defence mechanism. This analysis is aimed at the systematic profiling of DDVP to assess its cytotoxic and mutagenic potential for human vulnerability using an in silico classification model. DDVP was grouped into categories of analogue chemical compounds generated from inventories based on structural alerts that measure the biological effects on cell lines and animal models using the quantitative structure-activity relationship (QSAR) model. The cytotoxic and mutagenic potential of DDVP was assessed by analyzing target endpoints like skin sensitization, oral/inhalation toxicity, neurotoxicity and mutagenicity. DDVP shows moderate sensitization potential that can induce skin irritation during prolonged exposure because of the presence of dichlorovenyl side-chain that interacts with cellular proteins and causes degradation. 50% lethal dose (LD 50 ) of DDVP per body weight was determined to be 26.2 mg/kg in a rat model at 95% confidence range for acute oral toxicity, and 14.4 mmol/L was estimated as 50% lethal concentration (LC 50 ) in the atmosphere due to acute inhalation toxicity. DDVP can also inhibit acetylcholinesterase in the nervous system to produce nicotinic and muscarinic symptoms like nausea, vomiting, lacrimation, salivation, bradycardia, and respiratory failure may cause death. The widely used pesticide causes weak DNA methylation which can repress gene transcription on promoter sites. DDVP is volatile so it can cause oral and inhalation toxicity coupled with neurotoxicity during prolonged exposure. Serum cholinesterase blood tests should be encouraged in federal and state hospitals to investigate related health challenges as DDVP is still used in Nigeria.
Background: The world is currently facing the coronavirus disease-2019 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Researchers from different parts of the world have employed diverse approaches to create a safe and effective vaccine as it saves millions of lives. Vaccines are created from the viral particle to train the body for a natural defense against invading pathogens. It is important to understand the concept of the vaccine design, especially the multi-epitope T-cells subunit vaccine. Methods: In this regard, we employed bioinformatics and immunoinformatic tools to illustrate the concept of the computer-based vaccine design. The computational methods consist of evaluation and selection of SARS-CoV-2 structural proteins, prediction of cytotoxic T-lymphocyte (CTL) epitopes, prediction of helper T-cell (HTL) epitope, multi-epitope vaccine candidate construct, antigenicity and allergenicity prediction of the designed candidate vaccine, physiochemical properties and solubility evaluation, secondary/tertiary structure prediction, refinement and validation of model vaccine tertiary structure, molecular docking of fusion proteins and Toll-like receptor 9 protein, and in silico cloning of the vaccine. Results: A total of 454 amino acid sequences were generated from CTL and HTL epitopes. The query solubility value (QuerySol) of the vaccine construct was 0.419, including the human β-defensin-2 adjuvant and peptide linkers. A circular clone of vaccine and pEX-C-His plasmid was achieved after in silico ligation using the annealed primer. Conclusion: Here, we provide essential information on computer-assisted multi-epitopes T-cell subunit vaccine design.
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