BackgroundThe alarming increase in tick-borne pathogens such as human Babesia microti is an existential threat to global public health. It is a protozoan parasitic infection transmitted by numerous species of the genus Babesia. Second, monkeypox has recently emerged as a public health crisis, and the virus has spread around the world in the post-COVID-19 period with a very rapid transmission rate. These two novel pathogens are a new concern for human health globally and have become a significant obstacle to the development of modern medicine and the economy of the whole world. Currently, there are no approved drugs for the treatment of this disease. So, this research gap encourages us to find a potential inhibitor from a natural source.Methods and materialsIn this study, a series of natural plant-based biomolecules were subjected to in-depth computational investigation to find the most potent inhibitors targeting major pathogenic proteins responsible for the diseases caused by these two pathogens.ResultsAmong them, most of the selected natural compounds are predicted to bind tightly to the targeted proteins that are crucial for the replication of these novel pathogens. Moreover, all the molecules have outstanding ADMET properties such as high aqueous solubility, a higher human gastrointestinal absorption rate, and a lack of any carcinogenic or hepatotoxic effects; most of them followed Lipinski’s rule. Finally, the stability of the compounds was determined by molecular dynamics simulations (MDs) for 100 ns. During MDs, we observed that the mentioned compounds have exceptional stability against selected pathogens.ConclusionThese advanced computational strategies reported that 11 lead compounds, including dieckol and amentoflavone, exhibited high potency, excellent drug-like properties, and no toxicity. These compounds demonstrated strong binding affinities to the target enzymes, especially dieckol, which displayed superior stability during molecular dynamics simulations. The MM/PBSA method confirmed the favorable binding energies of amentoflavone and dieckol. However, further in vitro and in vivo studies are necessary to validate their efficacy. Our research highlights the role of Dieckol and Amentoflavone as promising candidates for inhibiting both monkeypox and Babesia microti, demonstrating their multifaceted roles in the control of these pathogens.

The Lassa virus (LASV), an RNA virus prevalent in West and Central Africa, causes severe hemorrhagic fever with a high fatality rate. However, no FDA-approved treatments or vaccines exist. Two crucial proteins, LASV glycoprotein and nucleoprotein, play vital roles in pathogenesis and are potential therapeutic targets. As effective treatments for many emerging infections remain elusive, cutting-edge drug development approaches are essential, such as identifying molecular targets, screening lead molecules, and repurposing existing drugs. Bioinformatics and computational biology expedite drug discovery pipelines, using data science to identify targets, predict structures, and model interactions. These techniques also facilitate screening leads with optimal drug-like properties, reducing time, cost, and complexities associated with traditional drug development. Researchers have employed advanced computational drug design methods such as molecular docking, pharmacokinetics, drug-likeness, and molecular dynamics simulation to investigate evodiamine derivatives as potential LASV inhibitors. The results revealed remarkable binding affinities, with many outperforming standard compounds. Additionally, molecular active simulation data suggest stability when bound to target receptors. These promising findings indicate that evodiamine derivatives may offer superior pharmacokinetics and drug-likeness properties, serving as a valuable resource for professionals developing synthetic drugs to combat the Lassa virus.

Delftia tsuruhatensis is an opportunistic pathogen, that causes human infection in immunocompromised individuals. The organism was found to be infectious in the respiratory tract and urinary tract infections. Isolation of D. tshuruhatensis showed resistance to common antibiotics, resulting in an alarming signal from the pathogen. Importantly, the D. tshuruhatensis strain was found to have the property of having IMP-1 Metallo-β-Lactamase, which could hydrolyze β-lactam antibiotics. To combat the challenge of antibiotic resistance, novel drug targets can be effective. For suggesting the novel drug targets, the entire proteome of D. tshuruhatensis strain TR1180 was subjected to subtractive genomic analysis using a variety of bioinformatic tools and servers. To identify human homologue proteins of the pathogen and proteins involved in common metabolic pathways between the pathogen and host, various bioinformatics tools and web servers were used. Only 62 proteins were found to be linked to pathogen-specific pathways; these proteins were then further screened to single out membrane-antigenic proteins that could be targeted by medications or vaccines. The novel therapeutic targets with the highest level of antigenicity were discovered to be ‘Nitrate transporter’ and ‘Phospho-N-acetylmuramoyl-pentapeptide-transferase’.