A synergistic therapy against influenza virus A/H1N1/PR8 by a HA1 specific neutralizing single-domain VL and an RNA hydrolyzing scFv
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 t...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1355599/full |
| _version_ | 1797201189222219776 |
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| author | Phuong Thi Hoang Phuong Thi Hoang Quynh Xuan Thi Luong Ramadhani Qurrota Ayun Yongjun Lee Kwang-Ji Oh Kwang-Ji Oh Taehyun Kim Taek-Kyun Lee Sukchan Lee |
| author_facet | Phuong Thi Hoang Phuong Thi Hoang Quynh Xuan Thi Luong Ramadhani Qurrota Ayun Yongjun Lee Kwang-Ji Oh Kwang-Ji Oh Taehyun Kim Taek-Kyun Lee Sukchan Lee |
| author_sort | Phuong Thi Hoang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T07:43:35Z |
| format | Article |
| id | doaj.art-7c52449fabae48fe876146560270803f |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-24T07:43:35Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-7c52449fabae48fe876146560270803f2024-04-19T05:08:51ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2024-04-011510.3389/fmicb.2024.13555991355599A synergistic therapy against influenza virus A/H1N1/PR8 by a HA1 specific neutralizing single-domain VL and an RNA hydrolyzing scFvPhuong Thi Hoang0Phuong Thi Hoang1Quynh Xuan Thi Luong2Ramadhani Qurrota Ayun3Yongjun Lee4Kwang-Ji Oh5Kwang-Ji Oh6Taehyun Kim7Taek-Kyun Lee8Sukchan Lee9Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, Republic of KoreaNovelgen Co., Ltd., R&D Center, Suwon-si, Gyeonggi-do, Republic of KoreaDepartment of Integrative Biotechnology, Sungkyunkwan University, Suwon, Republic of KoreaDepartment of Integrative Biotechnology, Sungkyunkwan University, Suwon, Republic of KoreaDepartment of Integrative Biotechnology, Sungkyunkwan University, Suwon, Republic of KoreaDepartment of Integrative Biotechnology, Sungkyunkwan University, Suwon, Republic of KoreaNovelgen Co., Ltd., R&D Center, Suwon-si, Gyeonggi-do, Republic of KoreaNovelgen Co., Ltd., R&D Center, Suwon-si, Gyeonggi-do, Republic of KoreaRisk Assessment Research Center, Korea Institute of Ocean Science and Technology, Geoje, Republic of KoreaDepartment of Integrative Biotechnology, Sungkyunkwan University, Suwon, Republic of KoreaThe 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.https://www.frontiersin.org/articles/10.3389/fmicb.2024.1355599/fullbio-panningsynergistic effectinfluenza virus3D8 scFvneutralizing antibodies |
| spellingShingle | Phuong Thi Hoang Phuong Thi Hoang Quynh Xuan Thi Luong Ramadhani Qurrota Ayun Yongjun Lee Kwang-Ji Oh Kwang-Ji Oh Taehyun Kim Taek-Kyun Lee Sukchan Lee A synergistic therapy against influenza virus A/H1N1/PR8 by a HA1 specific neutralizing single-domain VL and an RNA hydrolyzing scFv Frontiers in Microbiology bio-panning synergistic effect influenza virus 3D8 scFv neutralizing antibodies |
| title | A synergistic therapy against influenza virus A/H1N1/PR8 by a HA1 specific neutralizing single-domain VL and an RNA hydrolyzing scFv |
| title_full | A synergistic therapy against influenza virus A/H1N1/PR8 by a HA1 specific neutralizing single-domain VL and an RNA hydrolyzing scFv |
| title_fullStr | A synergistic therapy against influenza virus A/H1N1/PR8 by a HA1 specific neutralizing single-domain VL and an RNA hydrolyzing scFv |
| title_full_unstemmed | A synergistic therapy against influenza virus A/H1N1/PR8 by a HA1 specific neutralizing single-domain VL and an RNA hydrolyzing scFv |
| title_short | A synergistic therapy against influenza virus A/H1N1/PR8 by a HA1 specific neutralizing single-domain VL and an RNA hydrolyzing scFv |
| title_sort | synergistic therapy against influenza virus a h1n1 pr8 by a ha1 specific neutralizing single domain vl and an rna hydrolyzing scfv |
| topic | bio-panning synergistic effect influenza virus 3D8 scFv neutralizing antibodies |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1355599/full |
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