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Natural flavonoids effectively block the CD81 receptor of hepatocytes and inhibit HCV infection: a computational drug development approach

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Abstract

Hepatitis C virus (HCV) infection is a major public health concern, and almost two million people are infected per year globally. This is occurred by the diverse spectrum of viral genotypes, which are directly associated with chronic liver disease (fibrosis, and cirrhosis). Indeed, the viral genome encodes three principal proteins as sequentially core, E1, and E2. Both E1 and E2 proteins play a crucial role in the attachment of the host system, but E2 plays a more fundamental role in attachment. The researchers have found the "E2-CD81 complex" at the entry site, and therefore, CD81 is the key receptor for HCV entrance in both humans, and chimpanzees. So, the researchers are trying to block the host CD81 receptor and halt the virus entry within the cellular system via plant-derived compounds. Perhaps that is why the current research protocol is designed to perform an in silico analysis of the flavonoid compounds for targeting the tetraspanin CD81 receptor of hepatocytes. To find out the best flavonoid compounds from our library, web-based tools (Swiss ADME, pKCSM), as well as computerized tools like the PyRx, PyMOL, BIOVIA Discovery Studio Visualizer, Ligplot+ V2.2, and YASARA were employed. For molecular docking studies, the flavonoid compounds docked with the targeted CD81 protein, and herein, the best-outperformed compounds are Taxifolin, Myricetin, Puerarin, Quercetin, and (-)-Epicatechin, and outstanding binding affinities are sequentially − 7.5, − 7.9, − 8.2, − 8.4, and − 8.5 kcal/mol, respectively. These compounds have possessed more interactions with the targeted protein. To validate the post docking data, we analyzed both 100 ns molecular dynamic simulation, and MM-PBSA via the YASARA simulator, and finally finds the more significant outcomes. It is concluded that in the future, these compounds may become one of the most important alternative antiviral agents in the fight against HCV infection. It is suggested that further in vivo, and in vitro research studies should be done to support the conclusions of this in silico research workflow.

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Funding

This research was supported by Korea Institute of Oriental Medicine (Grant Number KSN2021240), Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2020R1I1A2066868), the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2020R1A5A2019413), a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant Number: HF20C0116), and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant Number: HF20C0038).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, 8100, Bangladesh

    Dipta Dey, Priyanka Paul, Abu Saim Mohammad Saikat & Babry Fatema

  2. Department of Genetic Engineering and Biotechnology, Faculty of Biological Science and Technology, Jashore University of Science and Technology (JUST), Jashore, 7408, Bangladesh

    Partha Biswas

  3. Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6204, Bangladesh

    Shafi Mahmud

  4. Department of Biochemistry and Microbiology, North South University, Dhaka, 1229, Bangladesh

    Tanzila Ismail Ema, Arysha Alif Khan & Shahlaa Zernaz Ahmed

  5. Department of Biochemistry and Molecular Biology, Faculty of Life Science, Mawlana Bhashani Science and Technology University, Tangail, Bangladesh

    Mohammad Mehedi Hasan

  6. Yunnan Herbal Laboratory, College of Ecology and Environmental Sciences, Yunnan University, Kunming, 650091, China

    Shabana Bibi

  7. Department of Biological Sciences, International Islamic University, Islamabad, Pakistan

    Shabana Bibi

  8. Global Biotechnology & Biomedical Research Network (GBBRN), Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia, 7003, Bangladesh

    Md. Ataur Rahman

  9. Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Korea

    Md. Ataur Rahman & Bonglee Kim

  10. Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Korea

    Md. Ataur Rahman & Bonglee Kim

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  1. Dipta Dey
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  2. Partha Biswas
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  3. Priyanka Paul
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  13. Bonglee Kim
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Contributions

Conceptualization: DD, and PB; Investigation, Data Curation, and Manuscript Writing: All authors; Visualization: DD, PB, PP, SM, MMH, BF, SB, MAR, BK; Writing-Review-Editing: DD, PB, BF, SB, MMH, MAR, BK; Supervision: MAR, and BK; Funding: BK All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Partha Biswas or Bonglee Kim.

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Dey, D., Biswas, P., Paul, P. et al. Natural flavonoids effectively block the CD81 receptor of hepatocytes and inhibit HCV infection: a computational drug development approach. Mol Divers 27, 1309–1322 (2023). https://doi.org/10.1007/s11030-022-10491-9

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  • DOI: https://doi.org/10.1007/s11030-022-10491-9

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