Computer-aided drug design of Azadirachta indica compounds against nervous necrosis virus by targeting grouper heat shock cognate protein 70 (GHSC70): quantum mechanics calculations and molecular dynamic simulation approaches

Abstract

Nervous necrosis virus (NNV) is a deadly infectious disease that affects several fish species. It has been found that the NNV utilizes grouper heat shock cognate protein 70 (GHSC70) to enter the host cell. Thus, blocking the virus entry by targeting the responsible protein can protect the fishes from disease. The main objective of the study was to evaluate the inhibitory potentiality of 70 compounds of Azadirachta indica (Neem plant) which has been reported to show potential antiviral activity against various pathogens, but activity against the NNV has not yet been reported. The binding affinity of 70 compounds was calculated against the GHSC70 with the docking and molecular dynamics (MD) simulation approaches. Both the docking and MD methods predict 4 (PubChem CID: 14492795, 10134, 5280863, and 11119228) inhibitory compounds that bind strongly with the GHSC70 protein with a binding affinity of –9.7, –9.5, –9.1, and –9.0 kcal/mol, respectively. Also, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of the compounds confirmed the drug-likeness properties. As a result of the investigation, it may be inferred that Neem plant compounds may act as significant inhibitors of viral entry into the host cell. More in-vitro testing is needed to establish their effectiveness.

High-throughput virtual screening of marine algae metabolites as high-affinity inhibitors of ISKNV major capsid protein: An analysis of in-silico models and DFT calculation to find novel drug molecules for fighting infectious spleen and kidney necrosis virus (ISKNV)

“…The compounds were first screened using a molecular docking procedure, and the top 4 compounds with binding affinities between −9.2 and −9.9 kcal/mol were selected for further in-silico process. All of the pharmacological analogs tested positive for significant hydrogen bond interactions with the MCP protein, showing that the drugs had an inhibitory activity [ 15 ]. For the chosen compounds, RO5 revealed their drug-like qualities [ 58 ].…”

“…Due to their low chemical reactivity and high kinetic stability, molecules that have a high FMO energy gap are more energetically stable than those that have a low FMO energy gap [ 46 ]. According to the findings of this research, the HOMO-LUMO gap energy of the compounds BC012, BC014, BS032, and RC009 that were chosen to be examined was much greater than expected, which indicates that the molecules are kinetically stable and have a low level of chemical reactivity [ 15 , 39 ].…”

“…To compute DFT, Becke's three parameters (B3LYP) and Lee-Yang-Parr functionals (B3LYP-D3) were combined with the dispersion correction energy term D3. The typical arrangement of capabilities B3LYP-D3 was selected for this study and 6-31G(d,p) was chosen to characterize the electronic wave function of the molecule [ 15 , 38 , 39 ]. Conventional B3LYP method have shown remarkable accuracy but one of the major limitations is its failure to accurately represent London Dispersion Interactions.…”

“…Therefore, the amount of time needed to conceive, create, and optimize a new medicine has been reduced due to advancements in silico drug design. For several decades, virtual screening has been used to identify the best lead compounds with a range of structural features for usage with a specific biological target [ 15 ]. Furthermore, computer-aided drug design has been used to identify, validate and explore various biological properties of marine metabolites including anti-inflammatory, anti-infectious, anti-cancer, antiviral, and anti-microbial effects via virtual screening, molecular docking, and dynamics modelling [ 16 , 17 ].…”