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Development of an effective single-chain variable fragment recognizing a novel epitope in the hepatitis C virus E2 protein that restricts virus entry into hepatocytes

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Abstract

Previously, we reported a neutralizing monoclonal antibody, A8A11, raised against a novel conserved epitope within the hepatitis C virus (HCV) E2 protein, that could significantly reduce HCV replication. Here, we report the nucleotide sequence of A8A11 and demonstrate the efficacy of a single-chain variable fragment (scFv) protein that mimics the antibody, inhibits the binding of an HCV virus-like particle to hepatocytes, and reduces viral RNA replication in a cell culture system. More importantly, scFv A8A11 was found to effectively restrict the increase of viral RNA levels in the serum of HCV-infected chimeric mice harbouring human hepatocytes. These results suggest a promising approach to neutralizing-antibody-based therapeutic interventions against HCV infection.

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Acknowledgments

We acknowledge the Department of Science and Technology, Ministry of Science and Technology (DST FIST), for support. So. D is supported by WoSA, DST. S.D acknowledges a J.C. Bose Fellowship from the Department of Science and Technology (DST), Government of India

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Authors and Affiliations

  1. Department of Biochemistry, Indian Institute of Science, Bangalore, 560012, India

    Soma Das, Dipeshwari J Shewale, Janhavi Bodele & Anjali A Karande

  2. Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India

    Padmanava Behera & Saumitra Das

  3. Centre For Human Genetics, Biotech Park, Bangalore, 560012, India

    Anjali A Karande

  4. National Institute of Biomedical Genomics, Kalyani, West Bengal, India

    Saumitra Das

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  1. Soma Das
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  2. Padmanava Behera
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Correspondence to Soma Das.

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The authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper.

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Communicated by Carolina Scagnolari

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Das, S., Behera, P., Shewale, D.J. et al. Development of an effective single-chain variable fragment recognizing a novel epitope in the hepatitis C virus E2 protein that restricts virus entry into hepatocytes. Arch Virol 169, 112 (2024). https://doi.org/10.1007/s00705-024-06024-4

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