Structural and Dynamical Basis of VP35-RBD Inhibition by Marine Fungi Compounds to Combat Marburg Virus Infection

Abstract

The Marburg virus (MBV), a deadly pathogen, poses a serious threat to world health due to the lack of effective treatments, calling for an immediate search for targeted and efficient treatments. In this study, we focused on compounds originating from marine fungi in order to identify possible inhibitory compounds against the Marburg virus (MBV) VP35-RNA binding domain (VP35-RBD) using a computational approach. We started with a virtual screening procedure using the Lipinski filter as a guide. Based on their docking scores, 42 potential candidates were found. Four of these compounds—CMNPD17596, CMNPD22144, CMNPD25994, and CMNPD17598—as well as myricetin, the control compound, were chosen for re-docking analysis. Re-docking revealed that these particular compounds had a higher affinity for MBV VP35-RBD in comparison to the control. Analyzing the chemical interactions revealed unique binding properties for every compound, identified by a range of Pi–cation interactions and hydrogen bond types. We were able to learn more about the dynamic behaviors and stability of the protein–ligand complexes through a 200-nanosecond molecular dynamics simulation, as demonstrated by the compounds’ consistent RMSD and RMSF values. The multidimensional nature of the data was clarified by the application of principal component analysis, which suggested stable conformations in the complexes with little modification. Further insight into the energy profiles and stability states of these complexes was also obtained by an examination of the free energy landscape. Our findings underscore the effectiveness of computational strategies in identifying and analyzing potential inhibitors for MBV VP35-RBD, offering promising paths for further experimental investigations and possible therapeutic development against the MBV.

Marine Brown Algae-Derived Compounds as Potential Inhibitors of Japanese Encephalitis Virus RNA-Dependent RNA Polymerase

“…Historically, marine organisms have been a rich source of bioactive compounds, with a notable track record in drug discovery [7]. Marine-derived molecules possess unique chemical structures not found in terrestrial compounds, which have been translated into therapeutic agents for a myriad of conditions, including viral infections [8][9][10][11]. Their diverse secondary metabolites, produced as chemical defenses against the complex marine environment, have provided novel scaffolds for developing antiviral agents [9].…”