Coronavirus disease 2019 (COVID-19) is an ongoing pandemic instigated by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which changed the daily train of the world’s population and cause several dead. Despite the significant efforts made in developing vaccines and therapeutic drugs, there is currently no available effective treatment against this new coronavirus infection, hence the need to continue research which is aimed at limiting the progression of this virus. The present study which has as objective to carry out in silico studies on the metabolites of some Cameroonian medicinal plants of the Asteraceae family with a view to propose potential molecules to fight against COVID-19. The selected plants are commonly used to treat respiratory infectious diseases, and for this reason they may contain some constituents which could exhibit an antiviral activity against SARS-CoV-2. In this work, a set of 74 naturally occurring compounds are computed with SARS-CoV-2 main protease protein (PDB ID: 6lu7) and spike protein (PDB ID: 6m0j) for their affinity and stability using binding energy analysis and molecular docking. Chrysoeriol-7-O-β-D-glucuronopyranoside (compound 16) has showed promising results including excellent Absorption, Distribution, Metabolism and Excretion (ADME) parameters as well as insignificant toxicity. Finally, the stability of this compound is complex with the two proteins validated through molecular dynamics (MD) simulation, they displayed stable trajectory and molecular properties with consistent interaction profile in molecular dynamics simulations. These findings call for further in vitro and in vivo challenges of phytoconstituents against the COVID-19 as a potential agent to fight the spread of this dramatic pandemic. Communicated by Ramaswamy H. Sarma

Huperzine A (HUP) plays a crucial role in Alzheimer’s therapy by enhancing cognitive function through increased cholinergic activity as a reversible acetylcholinesterase (AChE) inhibitor. Despite some limitations being seen in AChE inhibitors, ongoing research remains dedicated to finding innovative and more effective treatments for Alzheimer’s disease. To achieve the goal of the discovery of potential HUP analogues with improved physicochemical properties, less toxic properties, and high biological activity, many in silico methods were applied. Based on the acetylcholinesterase–ligand complex, an e-pharmacophore model was developed. Subsequently, a virtual screening involving a collection of 1762 natural compounds, sourced from the PubChem database, was performed. This screening yielded 131 compounds that exhibited compatibility with the established pharmacophoric hypothesis. These selected ligands were then subjected to molecular docking within the active site of the 4EY5 receptor. As a result, we identified four compounds that displayed remarkable docking scores and exhibited low free binding energy to the target. These top four compounds, CID_162895946, CID_44461278, CID_44285285, and CID_81108419, were submitted to ADMET prediction and molecular dynamic simulations, yielding encouraging findings in terms of their pharmacokinetic characteristics and stability. Finally, the molecular dynamic simulation, cross-dynamic correlation matrix, free energy landscape, and MM-PBSA calculations demonstrated that two ligands from the selected ligands formed very resilient complexes with the enzyme acetylcholinesterase, with significant binding affinity. Therefore, these two compounds are recommended for further experimental research as possible (AChE) inhibitors.

The discovery of antibacterials is considered one of the greatest medical achievements of all time. In this work, a combination of three computational analyzes: 3D-QSAR, molecular docking and ADME evaluation were applied in thienopyrimidine derivatives intended toward gram-positive bacterium Staphylococcus aureus. The validity of 3D-QSAR model was tested with a set of data which is divided into a training and a test set. The two models constructed (CoMFA and CoMSIA) show good statistical reliability (q2 = 0.758; r2 = 0.96; r2pred = 0.783) and (q2 = 0.744; r2 = 0.97; r2pred = 0.625) respectively. In addition, docking methods were applied to understand the structural features responsible for the affinity of the ligands in the binding of S. aureus DNA gyrase. Drug likeness and ADME analysis applied in this series of new proposed compounds, have shown that the five lead molecules would have the potential to be effective drugs and could be used as a starting point for designing compounds against Staphylococcus aureus.

Marine compounds constitute a diverse and invaluable resource for the discovery of bioactive substances with promising applications in the pharmaceutical development of anti-inflammatory and antibacterial agents. In this study, a comprehensive methodology was employed, encompassing pharmacophore modeling, virtual screening, in silico ADMET assessment (encompassing aspects of absorption, distribution, metabolism, excretion, and toxicity), and molecular dynamics simulations. These methods were applied to identify new inhibitors targeting the Hsp90 protein (heat shock protein 90), commencing with a diverse assembly of compounds sourced from marine origins. During the virtual screening phase, an extensive exploration was conducted on a dataset comprising 31,488 compounds sourced from the CMNPD database, characterized by a wide array of molecular structures. The principal objective was the development of structure-based pharmacophore models, a valuable approach when the pool of known ligands is limited. The pharmacophore model DDRRR was successfully constructed within the active sites of the Hsp90 crystal structure. Subsequent docking studies led to the identification of six compounds (CMNPD 22591, 9335, 10015, 360799, 15115, and 20988) demonstrating substantial binding affinities, each with values below −8.3 kcal/mol. In the realm of in silico ADMET predictions, five of these compounds exhibited favorable pharmacokinetic properties. Furthermore, molecular dynamics simulations and total binding energy calculations using MM-PBSA indicated that these marine-derived compounds formed exceptionally stable complexes with the Hsp90 receptor over a 100-nanosecond simulation period. These findings underscore the considerable potential of these novel marine compounds as promising candidates for anticancer and antimicrobial drug development.

FLT3 is considered a potential target of acute myeloid leukemia therapy. In this study, we applied a computer-aided methodology unifying molecular docking and pharmacophore screening to identify potent inhibitors against FLT3. To investigate the pharmacophore area and binding mechanism of FLT3, the reported co-crystallized Gilteritinib ligand was docked into the active site using Glide XP. Based on the docking results, we identified structure-based pharmacophore characteristics resistant to potent FLT3 inhibitors. The best hypothesis was corroborated using test and decoy sets, and the verified hypo was utilized to screen the chemical database. The hits from the pharmacophore-based screening were then screened again using a structure-based method that included molecular docking at various precisions; the selected molecules were further examined and refined using drug-like filters and ADMET analysis. Finally, two hits were picked out for molecular dynamic simulation. The results showed two hits were expected to have potent inhibitory activity and excellent ADMET characteristics, and they might be used as new leads in the development of FLT3 inhibitors. Communicated by Ramaswamy H. Sarma

Influenza represents a profoundly transmissible viral ailment primarily afflicting the respiratory system. Neuraminidase inhibitors constitute a class of antiviral therapeutics employed in the management of influenza. These inhibitors impede the liberation of the viral neuraminidase protein, thereby impeding viral dissemination from the infected cell to host cells. As such, neuraminidase has emerged as a pivotal target for mitigating influenza and its associated complications. Here, we apply a de novo hybridization approach based on a breed-centric methodology to elucidate novel neuraminidase inhibitors. The breed technique amalgamates established ligand frameworks with the shared target, neuraminidase, resulting in innovative inhibitor constructs. Molecular docking analysis revealed that the seven synthesized breed molecules (designated Breeds 1–7) formed more robust complexes with the neuraminidase receptor than conventional clinical neuraminidase inhibitors such as zanamivir, oseltamivir, and peramivir. Pharmacokinetic evaluations of the seven breed molecules (Breeds 1–7) demonstrated favorable bioavailability and optimal permeability, all falling within the specified parameters for human application. Molecular dynamics simulations spanning 100 nanoseconds corroborated the stability of these breed molecules within the active site of neuraminidase, shedding light on their structural dynamics. Binding energy assessments, which were conducted through MM-PBSA analysis, substantiated the enduring complexes formed by the seven types of molecules and the neuraminidase receptor. Last, the investigation employed a reaction-based enumeration technique to ascertain the synthetic pathways for the synthesis of the seven breed molecules.