Biology subjects

Islam, E.

Publications and source records attributed to Islam, E..

3 recordsLinked to original sources

bioRxiv2026

Multi-Target In Silico Investigation of Withaferin A as a Potential Antiviral Inhibitor Against Key Marburg Virus Proteins

Marburg virus (MARV) is a highly pathogenic filovirus that causes hemorrhagic fever with a high mortality rate, with very limited treatment options. The urgent need for targeted antiviral agents emphasizes the importance of structure-based drug discovery approaches. The present study aimed to evaluate the antiviral potential of Withaferin A (PubChem CID-265237) against three key proteins of MARV: viral protein 35 (VP35), and nucleoproteins (NP). Three-dimensional structures of these proteins were retrieved from RCSB-Protein Data Bank and docked with Withaferin A using AutoDock Vina. The ligand demonstrated favourable binding affinities towards all three viral targets, indicating strong interaction potential at functionally relevant sites. Drug-likeness and pharmacokinetic properties predicted using SwissADME and pkCSM indicated acceptable ADMET profiles that comply with key drug-like criteria. To validate the stability of the docking, molecular dynamics simulations (GROMACS, 100 nanoseconds) were conducted. The protein-ligand complexes exhibited stable root mean square deviation (RMSD), root mean square fluctuation (RMSF), and consistent hydrogen bonding patterns throughout the simulation. The MM-GBSA binding free energy analysis further supported favorable binding energetics, predominantly driven by van der Waals and electrostatic interactions. Altogether, these findings demonstrate that Withaferin A exhibits promising multi-target inhibitory potential against key MARV proteins. This study provides molecular insights into ligand-protein interactions and supports further experimental validation of Withaferin A as a potential therapeutic candidate against Marburg virus.

bioinformatics↗

bioRxiv2025

Structure-based engineering of a nutrient acquisition protein enhances neutralizing antibodies and protection for the development of a gonococcal vaccine

Gonorrhea is increasingly resistant to treatment and has been labelled an urgent threat due to the diminishing effectiveness of existing therapeutics. To address this challenge, we targeted the Neisseria gonorrhoeae transferrin binding protein B (TbpB), which is critical for iron acquisition and neisserial growth, as a vaccine target. Building on previous studies investigating the application of TbpB as an immunogen against various bacterial pathogens, we aimed to optimize this antigen for a broad protective effect. We compared the efficacy of wild type TbpB immunogens with engineered TbpB mutants that do not bind human transferrin (hTf) using infection studies in transgenic mice expressing hTf, which were required because the strict specificity of neisserial TbpB precludes its complexing with non-human transferrin. Comprehensive biophysical analyses confirmed that the introduced single residue mutations abolished hTf binding without compromising antigen structure. Immunization with the mutant antigens conferred increased resistance to infection by N. gonorrhoeae relative to that provided by the wild-type antigen in the humanized mice. When considering effector functions of the humoral response, we observed that the mutated antigen elicited more effective bactericidal and function-neutralizing activity. Through strategic mutations, we therefore enhanced vaccine effectiveness in a physiologically relevant model without significantly affecting the structure or immunogenicity of the antigen. This study highlights the use of rational structure-guided antigen design to drive effective immune responses and the potential interference of immunogen binding to host factors, and reinforces the utility of targeting TbpB in a gonococcal vaccine.

immunology↗

bioRxiv2024

Identification of potential inhibitors against Inosine 5'-Monophosphate Dehydrogenase of Cryptosporidium parvum through an integrated in silico approach

The protozoan parasite Cryptosporidium, found in several vertebrates, including humans, is the source of the global infection known as cryptosporidiosis, which manifests as acute gastroenteritis, abdominal pain, and diarrhea. Although infections in certain individuals have been linked to other species, Cryptosporidium parvum is the main cause of illnesses in humans. Lactate Dehydrogenase, Inosine 5'-Monophosphate Dehydrogenase (IMPDH), and several other targets have been identified by the genome sequencing of C. parvum. Bioactive phytochemicals derived from nature have enormous potential as anti-cryptosporidiosis agents. The study aimed to identify new anti-cryptosporidial agents that work against the IMPDH of the parasite by using integrated in silico approaches. In this study, a total of 24 bioactive phytochemicals were screened virtually through molecular docking and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analyses. Four lead compounds were identified, including Brevelin A (-8.9 kcal/mol), Vernodalin (-8.7 kcal/mol), Luteolin (-8.6 kcal/mol), and Pectolinarigenin (-8.1 kcal/mol), against the IMPDH protein (PDB ID: 4IXH) from the parasite. All the lead compounds had excellent pharmacokinetic and pharmacodynamic characteristics. The toxicity analysis showed satisfactory results with no major side effects. All of the selected compounds showed no violation of Lipinskis rules of five, indicating the possibility of oral bioavailability as potential drug candidates. In the majority of cases, target class prediction-identified enzymes, as well as investigational and experimental drugs, have been found to have structural similarities to the lead compounds. With significant biochemical interactions, all of the targeted phytochemical compounds have demonstrated excellent pharmacokinetics and better bioavailabilities. The findings strongly recommend in vitro experimental studies to aid in the development of novel therapeutics against Cryptosporidium parvum.

bioinformatics↗