Infection with the intracellular apicomplexan parasite Toxoplasma gondii causes serious clinical outcomes in both human and veterinary settings worldwide. Although approximately one-third of the world’s population is infected with T. gondii, an effective human vaccine for this disease remains unavailable. We aimed to design a potential T. gondii vaccine candidate that consisted of the B- and T-lymphocyte epitopes of three parasite immunogenic antigens. Firstly, the immunodominant epitopes expressed within the ROP2, MIC3, and GRA7 proteins of T. gondii were identified. Subsequently, six B-cell epitopes, five CTL epitopes, and five HTL epitopes were combined to generate a multi-epitope vaccine, and the 50S ribosomal protein L7/L12 was added as an adjuvant to boost the vaccine’s immunogenicity. All these epitopes were found to be antigenic, nonallergenic, nontoxic, and nonhuman homologs. The designed vaccine construct has a molecular weight of 51 kDa, an antigenicity score of 0.6182, and a solubility of 0.903461. Likewise, the candidate vaccine was immunogenic, nonallergenic, and stable. Molecular docking analysis revealed stable interactions between the vaccine construct and the TLR-4 immune receptor. Meanwhile, the stability of the developed vaccine was validated using molecular dynamics simulation. In silico, the vaccine construct was able to trigger primary immune responses. However, further laboratory-based assessments are needed to confirm its efficacy and safety.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal condition that encompasses ulcerative colitis (UC) and Crohn’s disease (CD). Targeting both inflammation and the epithelial barrier simultaneously can significantly improve symptom management in IBD, as a promising strategy. In this study, we focused on addressing both inflammation and the epithelial barrier. Until now, each therapeutic target including phosphodiesterase 4 (PDE4) and prolyl hydroxylase domain enzymes 1 and 2 (PHD1/2) have been studied separately. PDE4 plays a key role in the inflammatory process by converting cyclic AMP (cAMP) to AMP and its inhibition can suppress the production of inflammatory cytokines. Research has shown that inhibiting PHD1 and PHD2 increases levels of hypoxia-inducible factor-alpha (HIF-α), which in turn strengthens the epithelial barrier by promoting the expression of protective factors such as mucins and β-defensins. Through virtual screening, molecular docking, and molecular dynamics simulations, we identified five compounds—Cassiamin C, Ginkgetin, Hinokiflavone, Sciadopitysin, and Sojagol—as promising new drug candidates for IBD treatment. All compounds demonstrated superior free binding energy for the three targets compared to reference ligands, except Sojagol concerning PDE4B. Among these compounds, Ginkgetin was the best compound with potential ability of targeting multiple drug target proteins. Future experimental studies are warranted to validate these findings.

Rheumatoid arthritis (RA) is one of the most common inflammatory diseases in the world. Due to this importance, several drugs have been produced against effective targets in the pathogenesis of the disease. Considering various inflammatory pathways involved in RA, targeting each of these pathways alone cannot achieve sufficient improvement of the patients. Therefore, this study aimed to introduce safe natural product drug candidates screened in silico against several important protein targets (multi-targets) in the pathogenesis of RA. Tyrosine kinase 2 is a member of the Janus Kinase family, and due to its role in the signaling of numerous cytokines, its inhibition is considered an effective treatment option in inflammatory diseases. IL-6 is one of the most important innate immune cytokines that is secreted from activated macrophages in RA, and its level is directly related to the severity of joint destruction. Therefore, its inhibition plays an important role in improving the symptoms of RA. Also, the severity of the disease is directly related to the level of ACPA in the serum and synovial fluid of patients. Therefore, inhibiting its production by precluding the differentiation of B lymphocytes into plasma cells can improve the disease. In this study, after Virtual Screening, Molecular Docking, and Molecular Dynamics, we introduced Rutaecarpine, Hecogenin, Angustine, and Vomicine as new drug candidates for the treatment of RA. Rutaecarpine, Hecogenin, and Angustine inhibit all three targets with high affinity and stability, while Vomicine inhibits both TYK2 and IL-6 but not CD20. Future experimental studies can verify these findings.