Target-specificity of different amyrin subunits in impeding HCV influx mechanism inside the human cells considering the quantum tunnel profiles and molecular strings of the CD81 receptor: a combined in silico and in vivo study.
Anika JabinMohammad Fahim UddinSalauddin Al AzadAshfaque RahmanFawzia TabassumPritthy SarkerA K M Helal MorshedSamiur RahmanFatima Fairuz RaisaMusfiqur Rahman SakibAbeer Hasan OliveTabassum IslamRamisha TahsinShahlaa Zernaz AhmedPartha BiswasMst Umme HabibaMahbuba SiddiquyMaryam JafaryPublished in: In silico pharmacology (2023)
HCV is a hepatotropic RNA virus recognized for its frequent virulence and fatality worldwide. Despite many vaccine development programs underway, researchers are on a quest for natural bioactive compounds due to their multivalent efficiencies against viral infections, considering which the current research aimed to figure out the target-specificity and therapeutic potentiality of α, β, and δ subunits of amyrin, as novel bioactive components against the HCV influx mechanism. Initially, the novelty of amyrin subunits was conducted from 203 pharmacophores, comparing their in-silico pharmacokinetic and pharmacodynamic profiles. Besides, the best active site of CD81 was determined following the quantum tunneling algorithm. The molecular dynamic simulation was conducted (100 ns) following the molecular docking steps to reveal the parameters- RMSD (Å); Cα; RMSF (Å); MolSA (Å 2 ); Rg (nm); PSA (Å); SASA (Å 2 ), and the MM-GBSA dG binding scores. Besides, molecular strings of CD81, along with the co-expressed genes, were classified, as responsible for encoding CD81-mediated protein clusters during HCV infection, resulting in the potentiality of amyrins as targeted prophylactics in HCV infection. Finally, in vivo profiling of the oxidative stress marker, liver-specific enzymes, and antioxidant markers was conducted in the DMN-induced mice model, where β -amyrin scored the most significant values in all aspects.
Keyphrases
- hepatitis c virus
- molecular docking
- oxidative stress
- human immunodeficiency virus
- molecular dynamics simulations
- diabetic rats
- molecular dynamics
- genome wide
- nk cells
- staphylococcus aureus
- escherichia coli
- sars cov
- prostate cancer
- pseudomonas aeruginosa
- type diabetes
- photodynamic therapy
- public health
- single cell
- dna methylation
- single molecule
- transcription factor
- drug delivery
- biofilm formation
- insulin resistance
- metabolic syndrome
- signaling pathway
- dengue virus
- protein protein