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Monkeypox virus (MPXV) is a member of the Orthopoxvirus genus and the Poxviridae family, which instigated a rising epidemic called monkeypox disease. Proteinases are majorly engaged in viral propagation by catalyzing the cleavage of precursor polyproteins. Therefore, proteinase is essential for monkeypox and a critical drug target. In this study, high-throughput virtual screening (HTVS) and molecular dynamics simulation were applied to detect the potential natural compounds against the proteinase of the monkeypox virus. Here, 32,552 natural products were screened, and the top five compounds were selected after implementing the HTVS and molecular docking protocols in series. Gallicynoic Acid F showed the minimum binding score of −10.56 kcal/mole in the extra precision scoring method, which reflected the highest binding with the protein. The top five compounds showed binding scores ≤−8.98 kcal/mole. These compound complexes were tested under 100 ns molecular dynamics simulation, and Vaccinol M showed the most stable and consistent RMSD trend in the range of 2 Å to 3 Å. Later, MM/GBSA binding free energy and principal component analysis were performed on the top five compounds to validate the stability of selected compound complexes. Moreover, the ligands Gallicynoic Acid F and H2-Erythro-Neopterin showed the lowest binding free energies of −61.42 kcal/mol and −61.09 kcal/mol, respectively. Compared to the native ligand TTP-6171 (ΔGBind = −53.86 kcal/mol), these two compounds showed preferable binding free energy, suggesting inhibitory application against MPXV proteinase. This study proposed natural molecules as a therapeutic solution to control monkeypox disease.

The persistent global spread of dengue virus (DENV) necessitates the identification of novel antiviral therapeutics. The RNA-dependent RNA polymerase (RdRp) domain of the non-structural protein 5 (NS5) is a validated target for therapy due to its critical roles in viral genome replication. In this study, we used a structure-guided virtual screening approach to identify potent phytochemical inhibitors of DENV RdRp from the Plant Secondary Compound Database (PSC-db) by focusing on 326 flavonoids. Following drug-likeness filtering and hierarchical docking with MM-GBSA analysis, five top candidates were identified, with PSCdb01560 emerging as the most promising. Subsequent molecular dynamics simulations over 500 ns revealed PSCdb01560’s exceptional binding stability, characterised by low protein–ligand RMSD and sustained binding stability. Free energy landscape analysis demonstrated its occupation of deep, well-defined conformational basins. At the same time, post-MD MM-GBSA yielded a binding free energy of –91.65 kcal/mol—outperforming the reference compound. Structural superimposition confirmed strong conformational fidelity between docked and minimum-energy poses (RMSD 1.68 Å). Together, our approach points toward PSCdb01560 as the putative inhibitor molecule that outperforms existing flavonoid leads in thermodynamic and kinetic descriptors. The results thus provide the avenue for experimental validation, such as enzymatic and antiviral screens, in hopes of turning these in silico observations into viable therapeutic development for dengue.

Cholera, a life-threatening diarrheal disease caused by Vibrio cholerae, remains a global health concern. Traditional medicinal plants such as Berberis vulgaris (barberry) and Hydrastis canadensis (goldenseal) have long been used for their antimicrobial properties. This study employed integrated computational approaches to identify potential anti-cholera compounds from these plants by targeting sodium-pumping NADH-ubiquinone oxidoreductase (Na⁺-NQR). Virtual screening identified compounds 122623 , 197835 , and 638024 , along with the control Korormicin, exhibiting favorable binding affinities and hydrogen bonding interactions. Machine learning-based prediction models were further applied to assess functional activity and binding affinity. The study incorporated ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiling and density functional theory (DFT) calculations to evaluate physicochemical properties and electronic characteristics of the compounds. Molecular dynamics (MD) simulations demonstrated stable RMSD values for the ligands, with 122623 exhibiting the lowest RMSD (0.3–0.5 nm), closely resembling the control (0.3–0.4 nm), suggesting stable binding. Principal component analysis (PCA) showed tight conformational clusters for complexes with 122623 and 197835 , while free energy landscape (FEL) analysis revealed deep energy minima, supporting complex stability. MM/GBSA calculations showed that 122623 had the lowest binding free energy (-38.71 kcal/mol), followed by 638024 (-35.14 kcal/mol) and 197835 (-30.68 kcal/mol). Per-residue energy decomposition identified key residues (Phe137, Val155, Phe159, Phe160) involved in ligand binding. Network pharmacology analysis predicted additional gene targets for the selected compounds, providing insights into their broader therapeutic relevance. Collectively, compounds 122623 , 197835 , and 638024 derived from Hydrastis canadensis and Berberis vulgaris demonstrated promising inhibitory interactions with the Na⁺-NQR enzyme, suggesting their potential as anti-cholera agents.

The Zika virus (ZIKV), a member of the Flaviviridae family, has caused multiple widespread outbreaks, posing significant challenges to global health. This study explores the potential of compounds from Echinacea angustifolia ( E. angustifolia ) to inhibit the activity of ZIKV’s RNA-dependent RNA polymerase (RDRP), a key enzyme in the viral replication process and an ideal candidate for antiviral therapy. Utilizing computational techniques, we conducted a thorough virtual examination using the MTi-OpenScreen tool to identify potential RDRP inhibitors among E. angustifolia compounds. The top four compounds were further examined through re-docking procedures. To assess the robustness and effectiveness of these interactions, we performed molecular dynamics simulations along with calculations of the binding free energy and PCA analysis. This investigation highlighted four naturally occurring compounds, viz., Echinacoside, Rutin, Echinacin, and Cynaroside, demonstrating a notable affinity for binding to the allosteric site of ZIKV RDRP. These compounds showed strong hydrogen bond formation with crucial residues of the RDRP and presented favorable binding free energies. Our research sheds light on the viability of these E. angustifolia compounds as ZIKV RDRP inhibitors, laying a foundation for further experimental research in developing novel antiviral treatments against ZIKV infections.

The Ebola virus and its close relative, the Marburg virus, both belong to the family Filoviridae and are highly hazardous and contagious viruses. With a mortality rate ranging from 23% to 90%, depending on the specific outbreak, the development of effective antiviral interventions is crucial for reducing fatalities and mitigating the impact of Marburg virus outbreaks. In this investigation, a virtual screening approach was employed to evaluate 2042 natural compounds for their potential interactions with the VP35 protein of the Marburg virus. Average and worst binding energies were calculated for all 20 poses, and compounds that exhibited binding energies <−6 kcal/mol in both criteria were selected for further analysis. Based on binding energies, only six compounds (Estradiol benzoate, INVEGA (paliperidone), Isosilybin, Protopanaxadiol, Permethrin, and Bufalin) were selected for subsequent investigations, focusing on interaction analysis. Among these selected compounds, Estradiol benzoate, INVEGA (paliperidone), and Isosilybin showed strong hydrogen bonds, while the others did not. In this study, the compounds Myricetin, Isosilybin, and Estradiol benzoate were subjected to a molecular dynamics (MD) simulation and free binding energy calculation using MM/GBSA analysis. The reference component Myricetin served as a control. Estradiol benzoate exhibited the most stable and consistent root-mean-square deviation (RMSD) values, whereas Isosilybin showed significant fluctuations in RMSD. The compound Estradiol benzoate exhibited the lowest ΔG binding free energy (−22.89 kcal/mol), surpassing the control compound’s binding energy (−9.29 kcal/mol). Overall, this investigation suggested that Estradiol benzoate possesses favorable binding free energies, indicating a potential inhibitory mechanism against the VP35 protein of the Marburg virus. The study proposes that these natural compounds could serve as a therapeutic option for preventing Marburg virus infection. However, experimental validation is required to further corroborate these findings.

Middle East Respiratory Syndrome (MERS) is a viral respiratory disease caused b a special type of coronavirus called MERS-CoV. In the search for effective substances against the MERS-CoV main protease, we looked into compounds from brown algae, known for their medicinal benefits. From a set of 1212 such compounds, our computer-based screening highlighted four—CMNPD27819, CMNPD1843, CMNPD4184, and CMNPD3156. These showed good potential in how they might attach to the MERS-CoV protease, comparable to a known inhibitor. We confirmed these results with multiple computer tests. Studies on the dynamics and steadiness of these compounds with the MERS-CoV protease were performed using molecular dynamics (MD) simulations. Metrics like RMSD and RMSF showed their stability. We also studied how these compounds and the protease interact in detail. An analysis technique, PCA, showed changes in atomic positions over time. Overall, our computer studies suggest brown algae compounds could be valuable in fighting MERS. However, experimental validation is needed to prove their real-world effectiveness.

The World Health Organization (WHO) has designated the Zika virus (ZIKV) as a significant risk to the general public’s health. Currently, there are no vaccinations or medications available to treat or prevent infection with the Zika virus. Thus, it is urgently required to develop a highly efficient therapeutic molecule. In the presented study, a computationally intensive search was carried out to identify potent compounds that have the potential to bind and block the activity of ZIKV NS5 RNA-dependent RNA polymerase (RdRp). The anti-dengue chemical library was subjected to high-throughput virtual screening and MM/GBSA analysis in order to rate the potential candidates. The top three compounds were then chosen. According to the MM/GBSA analysis, compound 127042987 from the database had the highest binding affinity to the protein with a minimum binding free energy of −77.16 kcal/mole. Compound 127042987 had the most stable RMSD trend and the greatest number of hydrogen bond interactions when these chemical complexes were evaluated further under a 100 ns molecular dynamics simulation. Compound 127042987 displayed the best binding free energy (GBind) of −96.50 kcal/mol, surpassing the native ligand binding energy (−66.17 kcal/mole). Thereafter, an MM/GBSA binding free energy study was conducted to validate the stability of selected chemical complexes. Overall, this study illustrated that compound 127042987 showed preferred binding free energies, suggesting a possible inhibitory mechanism against ZIKV-RdRp. As per this study, it was proposed that compound 127042987 could be used as a therapeutic option to prevent Zika virus infection. These compounds need to be tested in experiments for further validation.

Head lice (Pediculus humanus capitis ) are a major global concern, and there is growing evidence of an increase in head lice prevalence among Saudi schoolchildren. The purpose of this study is to investigate the prevalence of an insecticidal resistance mutation in head lice collected from schoolchildren. A polymerase chain reaction (PCR) was used to amplify a segment of the voltage-gated sodium channel gene subunit to assess the prevalence and distribution of the kdr T917I mutation in head lice. Subsequently, the restriction fragment length polymorphism (RFLP) patterns revealed two genotypic forms: homozygous-susceptible (SS) and homozygous-resistant (RR). The results showed that 17 (37.80%) of the 45 samples were SS, whereas 28 (62.2%) were RR and T917I and L920F point mutations were found in the nucleotide and amino acid sequences of RR. Compared to other nations, the frequency of permethrin resistance mutation in the head louse population in Saudi Arabia was low. This study provides the first evidence of permethrin resistance mutation in human head lice in Saudi Arabia. The findings of this study will highlight the rising incidence of the kd r mutation in head lice in Saudi Arabia.

The escalating threat posed by the Monkeypox virus (MPXV) to global health necessitates the urgent discovery of effective antiviral agents, as there are currently no specific drugs available for its treatment, and existing inhibitors are hindered by toxicity and poor pharmacokinetic profiles. This study aimed to identify potent MPXV inhibitors by screening a diverse library of small molecule compounds derived from marine fungi, focusing on the viral protein VP39, a key methyltransferase involved in viral replication. An extensive virtual screening process identified four promising compounds—CMNPD15724, CMNPD28811, CMNPD30883, and CMNPD18569—alongside a control molecule. Rigorous evaluations, including re-docking, molecular dynamics (MD) simulations, and hydrogen bond analysis, were conducted to assess their inhibitory potential against MPXV VP39. CMNPD15724 and CMNPD30883, in particular, demonstrated a superior binding affinity and stable interactions within the target protein's active site throughout the MD simulations, suggesting a capacity to overcome the limitations associated with sinefungin. The stability of these VP39-compound complexes, corroborated by MD simulations, provided crucial insights into the dynamic behavior of these interactions. Furthermore, Principal Component Analysis (PCA) based free energy landscape assessments offered a detailed understanding of the dynamic conformational changes and energetic profiles underlying these compounds' functional disruption of VP39. These findings establish CMNPD15724, CMNPD28811, CMNPD30883, and CMNPD18569 as promising MPXV inhibitors and highlight marine fungi as a valuable source of novel antiviral agents. These compounds represent potential candidates for further experimental validation, advancing the development of safer and more effective therapeutic options to combat this emerging viral infection.

Helminth-derived proteins have immunomodulatory properties, influencing the host’s immune response as an adaptive strategy for helminth survival. Helminth-derived proteins modulate the immune response by inducing anti-inflammatory cytokines, promoting regulatory T-cell development, and ultimately favouring a Th2-biased immune response. This systematic review focused on helminth-derived proteins and explored their impact on reducing inflammatory responses in mouse models of colitis. A systematic search across Medline, EMBASE, Web of Science, and Cochrane Library identified fourteen relevant studies. These studies reported immunomodulatory changes, including increased production of anti-inflammatory cells and cytokines. In mouse models of colitis treated with on helminth-derived proteins, significant improvements in pathological parameters such as body weight, colon length, and microscopic inflammatory scores were observed compared to control groups. Moreover, helminth-derived proteins can enhance the function of Tregs and alleviate the severity of inflammatory conditions. The findings underscore the pivotal role of helminth-derived proteins in immunomodulation, specifically in the axis of cytokine secretion and immune cell polarization. The findings offer new opportunities for treating chronic inflammatory conditions such Crohn’s disease.