Exploring therapeutic potential of Carissa carandas for Typhoid: An integrated approach using molecular docking, MD simulation, MMGBSA, and ADMET analysis

Typhoid fever, caused by Salmonella typhi, continues to pose a significant global health challenge, particularly with the increasing prevalence of multidrug-resistant strains. Despite ongoing vaccination efforts, typhoid fever still accounts for over 9 million infections and more than 110,000 deaths annually, predominantly affecting low- and middle-income countries. This persistent burden, coupled with the rise of antibiotic resistance, underscores an urgent need for alternative therapeutic strategies. In response, this study investigates the therapeutic potential of phytochemicals derived from Carissa carandas, a novel and underexplored medicinal plant traditionally used in ethnomedicine, through an integrated computational approach. A comprehensive library of 143 phytochemicals was assembled and rigorously screened using Lipinski’s rule of five and ADMET parameters, which led to the identification of 42 promising candidates for further evaluation. Molecular docking studies revealed that key compounds including Ursolic acid, carissic acid, and 3-hydroxyurs-12-en-28-oic acid exhibited binding affinities of approximately –9.6, –9.4, and –9.6 kcal/mol, respectively, significantly outperforming ciprofloxacin, which showed a binding affinity of –7.0 kcal/mol. To further assess the stability of these interactions, molecular dynamics simulations were conducted over a 100 ns period. The results demonstrated outstanding structural stability of the Ursolic acid–OmpF complex, as evidenced by a strong network of hydrogen bonds throughout the simulation and minimal root-mean-square deviation (RMSD) fluctuations. Because Ursolic acid strongly interacts with the target protein, complementary MMGBSA analysis produced a total binding energy of –32.35 ± 2.87 kcal/mol. Furthermore, ADMET profiling confirmed that the lead compounds possess certain favorable pharmacokinetic properties and safety profiles and have improved drug-likeness scores relative to ciprofloxacin. These numerical outcomes suggest that C. carandas-derived compounds represent a promising phytotherapeutic approach for managing typhoid fever; therefore, further tests using both in vitro and in vivo setups are necessary to confirm this.