A synergistic therapy against influenza virus A/H1N1/PR8 by a HA1 specific neutralizing single-domain VL and an RNA hydrolyzing scFv
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Title
- A synergistic therapy against influenza virus A/H1N1/PR8 by a HA1 specific neutralizing single-domain VL and an RNA hydrolyzing scFv
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Author(s)
- Hoang, Phuong Thi; Luong, Quynh Xuan Thi; Ayun, Ramadhani Qurrota; Lee, Yongjun; Oh, Kwang-Ji; Kim, Taehyun; Lee, Taek Kyun; Lee, Sukchan
- KIOST Author(s)
- Lee, Taek Kyun(이택견)
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Alternative Author(s)
- 이택견
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Publication Year
- 2024-04
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Abstract
- The emergence of anti-influenza drug-resistant strains poses a challenge for influenza therapy due to mutations in the virus’s surface protein. Recently, there has been increasing interest in combination therapy consisting of two or more drugs as a potential alternative approach, aiming to enhance therapeutic efficacy. In this study, we investigated a novel synergistic therapy with a vertical effect using a single-domain VL-HA1-specific antibody against H1N1/PR8 and a horizontal effect using an RNA catalytic antibody with broad-spectrum influenza antiviral drug. We isolated a single-domain VL-HA1-specific (NVLH8) antibody binding to the virus particles showing a neutralizing activity against influenza virus A, specifically H1N1/PR8, as determined by the reduction in plaque number and lower viral HA protein expression in vitro. The neutralizing antibody likely prevented the viral entry, specifically at the viral genome-releasing step. Additionally, the 3D8 scFv hydrolyzed viral RNAs in the cytoplasm, including mRNA, vRNA, and cRNA in MDCK cells. The combined treatment of neutralizing antibodies for a vertical effect and 3D8 scFv for a horizontal effect produced a synergistic effect providing a novel approach against viral diseases when compared with a single treatment. Our results indicated that combining treatment, in particular two proteins exhibiting different mechanisms of action increased the antiviral activity against the influenza virus.
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ISSN
- 1664-302X
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URI
- https://sciwatch.kiost.ac.kr/handle/2020.kiost/45530
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DOI
- 10.3389/fmicb.2024.1355599
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Bibliographic Citation
- Frontiers in Microbiology, v.15, 2024
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Publisher
- Frontiers Media S.A.
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Keywords
- neutralizing antibodies; bio-panning; synergistic effect; influenza virus; 3D8 scFv
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Type
- Article
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Language
- English
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