Mpox (formerly known as monkeypox) virus and some related poxviruses including smallpox virus pose a significant threat to public health, and effective prevention and treatment strategies are needed. This study utilized a reverse vaccinology approach to retrieve conserved epitopes for monkeypox virus and construct a vaccine that could provide cross-protection against related viruses with similar antigenic properties. The selected virulent proteins of monkeypox virus, MPXVgp165, and Virion core protein P4a, were subjected to epitope mapping for vaccine construction. Two vaccines were constructed using selected T cell epitopes and B cell epitopes with PADRE and human beta-defensins adjuvants conjugated in the vaccine sequence. Both constructs were found to be highly antigenic, non-allergenic, nontoxic, and soluble, suggesting their potential to generate an adequate immune response and be safe for humans. Vaccine construct 1 was selected for molecular dynamic simulation studies. The simulation studies revealed that the TLR8-vaccine complex was more stable than the TLR3-vaccine complex. The lower RMSD and RMSF values of the TLR8 bound vaccine compared to the TLR3 bound vaccine suggested better stability and consistency of hydrogen bonds. The Rg values of the vaccine chain bound to TLR8 indicated overall stability, whereas the vaccine chain bound to TLR3 showed deviations throughout the simulation. These results suggest that the constructed vaccine could be a potential preventive measure against monkeypox and related viruses however, further experimental validation is required to confirm these findings.
The Varicella Zoster Virus (VZV) presents a global health challenge due to its dual manifestations of chickenpox and shingles. Despite vaccination efforts, incomplete coverage, and waning immunity lead to recurrent infections, especially in aging and immunocompromised individuals. Existing vaccines prevent chickenpox but can trigger the reactivation of shingles. To address these limitations, we propose a polyvalent multiepitope subunit vaccine targeting key envelope glycoproteins of VZV. Through bioinformatics approaches, we selected six glycoproteins that are crucial for viral infection. Epitope mapping led to the identification of cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B cell linear (LBL) epitopes. Incorporating strong immunostimulants, we designed two vaccine constructs, demonstrating high antigenicity, solubility, stability, and compatibility with Toll-like receptors (TLRs). Molecular docking and dynamics simulations underscored the stability and affinity of the vaccine constructs with TLRs. These findings lay the foundation for a comprehensive solution to VZV infections, addressing the challenges of incomplete immunity and shingles reactivation. By employing advanced immunoinformatics and dynamics strategies, we have developed a promising polyvalent multiepitope subunit vaccine candidate, poised to enhance protection against VZV and its associated diseases. Further validation through in vivo studies is crucial to confirm the effectiveness and potential of the vaccine to curb the spread of VZV. This innovative approach not only contributes to VZV control but also offers insights into tailored vaccine design strategies against complex viral pathogens.
Rhizoctonia solani , the causative agent of sheath blight disease in rice, poses a significant threat to agricultural productivity. Traditional management approaches involving chemical fungicides have been effective but come with detrimental consequences for the ecosystem. This study aimed to investigate sustainable alternatives in the form of antifungal peptides derived from Solanaceous plant species as potential agents against R . solani . Peptide extracts were obtained using an optimized antimicrobial peptide (AMP) extraction method and desalted using the solid-phase extraction technique. The antifungal potential of peptide-rich extracts from Solanum tuberosum and Capsicum annum was assessed through in vitro tests employing the agar well diffusion method. Furthermore, peptide-protein docking analysis was performed on HPEPDOCK and HDOCK server; and molecular dynamics simulations (MDS) of 100 ns period were performed using the Gromacs 2020.4. The results demonstrated significant inhibition zones for both extracts at concentrations of 100 mg/mL. Additionally, the extracts of Solanum tuberosum and Capsicum annum had minimum inhibitory concentrations of 50 mg/mL and 25 mg/mL, respectively with minimum fungicidal concentrations of 25 mg/mL. Insights into the potential mechanisms of key peptides inhibiting R . solani targets were gleaned from in-silico studies. Notably, certain AMPs exhibited favorable free energy of binding against pathogenicity-related targets, including histone demethylase, sortin nexin, and squalene synthase, in protein-peptide docking simulations. Extended molecular dynamics simulations lasting 100 ns and MM-PBSA calculations were performed on select protein-peptide complexes. AMP10 displayed the most favorable binding free energy against all target proteins, with AMP3, AMP12b, AMP6, and AMP15 also exhibiting promising results against specific targets of R . solani . These findings underscore the potential of peptide extracts from S . tuberosum and C . annum as effective antifungal agents against rice sheath blight caused by R . solani .
Human T-lymphotropic virus (HTLV), a group of retroviruses belonging to the oncovirus family, has long been associated with various inflammatory and immunosuppressive disorders. At present, there is no approved vaccine capable of effectively combating all the highly pathogenic strains of HTLV that makes this group of viruses a potential threat to human health. To combat the devastating impact of any potential future outbreak caused by this virus group, our study employed a reverse vaccinology approach to design a novel polyvalent vaccine targeting the highly virulent subtypes of HTLV. Moreover, we comprehensively analyzed the molecular interactions between the designed vaccine and corresponding Toll-like receptors (TLRs), providing valuable insights for future research on preventing and managing HTLV-related diseases and any possible outbreaks. The vaccine was designed by focusing on the envelope glycoprotein gp62, a crucial protein involved in the infectious process and immune mechanisms of HTLV inside the human body. Epitope mapping identified T cell and B cell epitopes with low binding energies, ensuring their immunogenicity and safety. Linkers and adjuvants were incorporated to enhance the vaccine's stability, antigenicity, and immunogenicity. Initially, two vaccine constructs were formulated, and among them, vaccine construct-2 exhibited superior solubility and structural stability. Molecular docking analyses also revealed strong binding affinity between the vaccine construct-2 and both targeted TLR2 and TLR4. Molecular dynamics simulations demonstrated enhanced stability, compactness, and consistent hydrogen bonding within TLR-vaccine complexes, suggesting a strong binding affinity. The stability of the complexes was further corroborated by contact, free energy, structure, and MM-PBSA analyses. Consequently, our research proposes a vaccine targeting multiple HTLV subtypes, offering valuable insights into the molecular interactions between the vaccine and TLRs. These findings should contribute to developing effective preventive and treatment approaches against HTLV-related diseases and preventing possible outbreaks. However, future research should focus on in-depth validation through experimental studies to confirm the interactions identified in silico and to evaluate the vaccine's efficacy in relevant animal models and, eventually, in clinical trials.
Breast cancer, a deadly disease among women, demands effective interventions due to its global impact, with over one million annual cases. Current anti-breast cancer drugs displays several side effects, also most patients resists to these drugs during early treatment stage. Hence, global search for better drugs with less side effects became necessary. The objective of this study is to identify potential inhibitors of vascular endothelial growth factor receptor-2 (VEGFR-2), a critical target in breast cancer treatment. Molecular docking-based virtual screening of 45 benzoxazole/thiazole derivatives was conducted, followed by molecular dynamics simulations to explore ligand-protein interactions. Seven ligands (compounds 7, 10, 12, 13, 14, 20, and 26) demonstrated superior binding affinities ranging from −157.85 to −173.88 kcal/mol (MolDock scores) and −109.96 to −129.23 kcal/mol (Re-rank scores) compared to Sorafenib (−156.35 kcal/mol MolDock score and −102.63 kcal/mol Re-rank score). Compound 7, identified as a potential hit, exhibited stability in a 100-ns dynamic simulation. It was chosen as a template for designing novel inhibitors, resulting in five compounds with improved binding affinities ranging from −177.84 to −184.69 kcal/mol (MolDock scores) and −137.34 to −143.44 kcal/mol (Re-rank scores). Pharmacological profiling confirmed the drug-like properties of both the potential hit molecules and the designed compounds, with 0–1 violations against Lipinski's rule of five and favorable pharmacokinetics status. Density functional theory (DFT) studies illustrated the reactive nature of the designed compounds. These findings suggest the potential of these molecules as novel VEGFR-2 inhibitors for breast cancer treatment, providing promising prospects for future drug development.
Abstract Human T-lymphotropic virus (HTLV), a retrovirus belonging to the oncovirus family, has long been linked to be associated with various inflammatory and immunosuppressive disorders. To combat the devastating impact of this virus, our study employed a reverse vaccinology approach to design a multi-epitope-based vaccine targeting the highly virulent subtypes of HTLV. We conducted a comprehensive analysis of the molecular interactions between the vaccine and Toll-like receptors (TLRs), providing valuable insights for future research on preventing and managing HTLV-related diseases and any possible outbreaks. The vaccine was designed by focusing on the envelope glycoprotein gp62, a crucial protein involved in the infectious process and immune mechanisms of HTLV inside the human body. Epitope mapping identified T cell and B cell epitopes with low binding energies, ensuring their immunogenicity and safety. Linkers and adjuvants were incorporated to enhance the vaccine’s stability, antigenicity, and immunogenicity. Two vaccine constructs were developed, both exhibiting high antigenicity and conferring safety. Vaccine construct 2 demonstrated expected solubility and structural stability after disulfide engineering. Molecular docking analyses revealed strong binding affinity between the vaccine construct 2 and both TLR2 and TLR4. Molecular dynamics simulations indicated that the TLR2-vaccine complex displayed enhanced stability, compactness, and consistent hydrogen bond formation, suggesting a favorable affinity. Contact analysis, Gibbs free energy landscapes, and DCC analysis further supported the stability of the TLR2-vaccine complex, while DSSP analysis confirmed stable secondary structures. MM-PBSA analysis revealed a more favorable binding affinity of the TLR4-vaccine complex, primarily due to lower electrostatic energy. In conclusion, our study successfully designed a multi-epitope-based vaccine targeting HTLV subtypes and provided valuable insights into the molecular interactions between the vaccine and TLRs. These findings should contribute to the development of effective preventive and treatment approaches against HTLV-related diseases.
• please read through all the templates before choosing • pick the most relevant text template(s) from the following page and delete all others. • edit the text as necessary, ensuring that the original incorrect text is included for the record, please see the below. • please do not use any extra formatting when editing the templates, and only modify the red text unless absolutely necessary • submit to Frontiers following the instructions on this page.When the original text contained incorrect information, to preserve the scientific record, please include that text when editing the below templates. For example:There was a mistake in the Funding statement, an incorrect number was used. The correct number is "2015C03Bd051.". The publisher apologizes for this mistake.The original version of this article has been updated. Corrigendum on: Amin Rani N, Moin AT, Patil R, Barketullah Robin T, Zubair T, Nawal N, Sami MRS, Morshed MM, Zhai J, Xue M, Hossain M, Zheng C, Abul Manchur M and Islam NN (2023) Designing a polyvalent vaccine targeting multiple strains of varicella zoster virus using integrated bioinformatics approaches. Front. Microbiol. 14:1291868. doi: 10.3389/fmicb.2023.1291868 In the published article, there was an error in the Acknowledgement statement. [In the Acknowledgment, we mentioned several individuals and organizations as a token of appreciation. However, this might lead readers to mistakenly believe that these individuals and organizations funded our study. We want to make it clear that our study did not receive any funding from any internal or external sources. To prevent any confusion, we kindly ask for your assistance in removing the names from the Acknowledgment section from the published article.]. The correct Acknowledgement statement appears below.[We dedicate this study to the aspiring student researchers of Bangladesh, whose passion for science and research holds the promise of making remarkable contributions to the field.]The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.End of template, if you would like to request a correction for a reason not seen here, please contact the journal's Editorial Office
Abstract Despite being a promising phytochemical, Curcumin’s potential applications are limited due to its classification in BCS class IV, which is associated with low water solubility and permeability. Enhancing the bioavailability of BCS class IV drugs presents a significant challenge, but crystal chemistry provides a hopeful avenue for overcoming this hurdle. In this research, co-crystals of Curcumin were developed to improve both solubility and permeability. Unlike traditional methods that require extensive trial-based lab work and time-consuming screening of co-formers, the use of molecular docking in In-silico co-former screening offers a scientific and rational approach to selecting suitable partners. In this study, two distinct co-crystals were synthesized using a solvent evaporation technique with methanol as the solvent, employing a 1:1 molar ratio. L-proline and piperine were chosen as co-formers to enhance solubility and permeability, respectively. The co-crystals underwent optimization and characterization through Design of Experiments (DOE). Comparing the dissolution study results for the same curcumin concentration, the cumulative drug release (CDR) after 8 hours was 20% for pure curcumin and an impressive 71% for curcumin-L-proline co-crystals. The permeability study, conducted over four hours using the everted gut sac method in phosphate buffer pH 6.8, revealed curcumin’s permeability to be less than 0.05 mg/mL, while curcumin-piperine co-crystals exhibited a five-fold increase (0.2545 mg/mL) in permeability. The co-crystals formed through a molecular ratio of 1:1 for curcumin-L-proline to enhance solubility and 1:1 for curcumin-piperine to enhance permeability, both demonstrated positive outcomes with support from optimization analysis, FTIR, DSC, SEM, PXRD analysis, and dissolution studies.
'%3e%3ccircle r='20' fill='%23008'/%3e%3ccircle r='17.5' fill='%23fff'/%3e%3ccircle r='3.5' fill='%23008'/%3e%3cg id='d'%3e%3cg id='c'%3e%3cg id='b'%3e%3cg id='a' fill='%23008'%3e%3ccircle r='.875' transform='rotate(7.5 -8.75 133.5)'/%3e%3cpath d='M0 17.5.6 7 0 2l-.6 5L0 17.5z'/%3e%3c/g%3e%3cuse xlink:href='%23a' transform='rotate(15)'/%3e%3c/g%3e%3cuse xlink:href='%23b' transform='rotate(30)'/%3e%3c/g%3e%3cuse xlink:href='%23c' transform='rotate(60)'/%3e%3c/g%3e%3cuse xlink:href='%23d' transform='rotate(120)'/%3e%3cuse xlink:href='%23d' transform='rotate(-120)'/%3e%3c/g%3e%3c/svg%3e)
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)