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

  • In Silico Pharmacol. 2023 Mar 29;11(1):8. doi: 10.1007/s40203-023-00144-6.
Anika Jabin  1 ,  Mohammad Fahim Uddin  2 ,  Salauddin Al Azad  3 ,  Ashfaque Rahman  1 ,  Fawzia Tabassum  4 ,  Pritthy Sarker  1 ,  A K M Helal Morshed  5 ,  Samiur Rahman  1 ,  Fatima Fairuz Raisa  6 ,  Musfiqur Rahman Sakib  7 ,  Abeer Hasan Olive  8 ,  Tabassum Islam  9 ,  Ramisha Tahsin  10 ,  Shahlaa Zernaz Ahmed  1 ,  Partha Biswas  11 ,  Mst Umme Habiba  12 ,  Mahbuba Siddiquy  13 ,  Maryam Jafary  14
Affiliations
  • 1. Department of Biochemistry and Microbiology, North South University, Dhaka, 1229 Bangladesh.
  • 2. College of Material Science and Engineering, Zhejiang Sci-Tech University, Hangzhou, 310018 Zhejiang People's Republic of China.
  • 3. Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122 Jiangsu Province People's Republic of China.
  • 4. Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet, 3114 Bangladesh.
  • 5. Pathology and Pathophysiology Major, Academy of Medical Science, Zhengzhou University, Zhengzhou City, 450001 Henan Province People's Republic of China.
  • 6. Department of Electrical and Electronic Engineering, Brac University, Dhaka, 1212 Bangladesh.
  • 7. Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, 8100 Bangladesh.
  • 8. Department of Pharmacy, East West University, Dhaka, 1212 Bangladesh.
  • 9. Department of Computer Science and Engineering, East West University, Dhaka, 1212 Bangladesh.
  • 10. Department of Pharmaceutical Sciences, North South University, Dhaka, 1229 Bangladesh.
  • 11. Department of Genetic Engineering and Biotechnology, Jashore University of Science and Technology, Jashore, 7408 Bangladesh.
  • 12. Data Science Research Unit, RPG Interface Lab, Jashore, 7400 Bangladesh.
  • 13. State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122 Jiangsu Province People's Republic of China.
  • 14. Division of Food Safety and Hygiene, Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, 1416634793 Iran.
PMID: 36999133 DOI: 10.1007/s40203-023-00144-6
Abstract

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 (Å2); Rg (nm); PSA (Å); SASA (Å2), 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.

Keywords
CD81 receptor; Co-expressed genes behind HCV invasion; DMN-induced hepatic fibrosis; HCV infection; In-silico pharmacokinetics and pharmacodynamics; Target-specificity of amyrins.
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