Antiviral Activity, Pharmacoinformatics, Molecular Docking, and Dynamics Studies of Azadirachta indica Against Nipah Virus by Targeting Envelope Glycoprotein: Emerging Strategies for Developing Antiviral Treatment.
Md Mizanur RahamanNoimul Hasan SiddiqueeRahima AkterNikkon SarkerUditi Paul BristiKhandokar Fahmida SultanaSm Lutfor Rahman RemonAfroza SultanaTushar Ahmed ShishirMd Mizanur RahamanFiroz AhmedFoysal HossenMohammad Ruhul AminMir Salma AkterPublished in: Bioinformatics and biology insights (2024)
The Nipah virus (NiV) belongs to the Henipavirus genus is a serious public health concern causing numerous outbreaks with higher fatality rate. Unfortunately, there is no effective medication available for NiV. To investigate possible inhibitors of NiV infection, we used in silico techniques to discover treatment candidates in this work. As there are not any approved treatments for NiV infection, the NiV-enveloped attachment glycoprotein was set as target for our study, which is responsible for binding to and entering host cells. Our in silico drug design approach included molecular docking, post-docking molecular mechanism generalised born surface area (MM-GBSA), absorption, distribution, metabolism, excretion/toxicity (ADME/T), and molecular dynamics (MD) simulations. We retrieved 418 phytochemicals associated with the neem plant ( Azadirachta indica ) from the IMPPAT database, and molecular docking was used to ascertain the compounds' binding strength. The top 3 phytochemicals with binding affinities of -7.118, -7.074, and -6.894 kcal/mol for CIDs 5280343, 9064, and 5280863, respectively, were selected for additional study based on molecular docking. The post-docking MM-GBSA of those 3 compounds was -47.56, -47.3, and -43.15 kcal/mol, respectively. As evidence of their efficacy and safety, all the chosen drugs had favorable toxicological and pharmacokinetic (Pk) qualities. We also performed MD simulations to confirm the stability of the ligand-protein complex structures and determine whether the selected compounds are stable at the protein binding site. All 3 phytochemicals, Quercetin (CID: 5280343), Cianidanol (CID: 9064), and Kaempferol (CID: 5280863), appeared to have outstanding binding stability to the target protein than control ribavirin, according to the molecular docking, MM-GBSA, and MD simulation outcomes. Overall, this work offers a viable approach to developing novel medications for treating NiV infection.
Keyphrases
- molecular docking
- molecular dynamics
- molecular dynamics simulations
- density functional theory
- public health
- binding protein
- protein protein
- healthcare
- induced apoptosis
- adverse drug
- oxidative stress
- type diabetes
- dna binding
- transcription factor
- drug induced
- electronic health record
- cell cycle arrest
- preterm infants
- cell death
- endoplasmic reticulum stress
- weight loss