In vitro and in silico investigation of effects of antimicrobial peptides from Solanaceae plants against rice sheath blight pathogen Rhizoctinia solani.

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.

In-silico formulation of a next-generation polyvalent vaccine against multiple strains of monkeypox virus and other related poxviruses.

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.

Designing a polyvalent vaccine targeting multiple strains of varicella zoster virus using integrated bioinformatics approaches.

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.

Correction: An immunoinformatics and extended molecular dynamics approach for designing a polyvalent vaccine against multiple strains of Human T-lymphotropic virus (HTLV).

[This corrects the article DOI: 10.1371/journal.pone.0287416.].

An immunoinformatics and extended molecular dynamics approach for designing a polyvalent vaccine against multiple strains of Human T-lymphotropic virus (HTLV).

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.

An accidental finding of a retroperitoneal desmoid tumor: case report and review of the literature.

Retroperitoneal desmoid-type fibromatosis is a rare benign mesenchymal neoplasm that develops as a result of fibroblastic proliferation within the musculoaponeurotic stroma. The authors present the case of a 41-year-old male patient who was referred for a retroperitoneal neoplasm. A mesenteric mass core biopsy was done, and it revealed a low-grade spindle cell lesion consistent with desmoid fibromatosis.