tetano
Editor, Senior Moderator
Front Microbiol
. 2024 Apr 19:15:1355599.
doi: 10.3389/fmicb.2024.1355599. eCollection 2024. A synergistic therapy against influenza virus A/H1N1/PR8 by a HA1 specific neutralizing single-domain V[SUB]L[/SUB] and an RNA hydrolyzing scFv
Phuong Thi Hoang[SUP] 1 2 [/SUP], Quynh Xuan Thi Luong[SUP] 1 [/SUP], Ramadhani Qurrota Ayun[SUP] 1 [/SUP], Yongjun Lee[SUP] 1 [/SUP], Kwang-Ji Oh[SUP] 1 2 [/SUP], Taehyun Kim[SUP] 2 [/SUP], Taek-Kyun Lee[SUP] 3 [/SUP], Sukchan Lee[SUP] 1 [/SUP]
Affiliations
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.
Keywords: 3D8 scFv; bio-panning; influenza virus; neutralizing antibodies; synergistic effect.
. 2024 Apr 19:15:1355599.
doi: 10.3389/fmicb.2024.1355599. eCollection 2024. A synergistic therapy against influenza virus A/H1N1/PR8 by a HA1 specific neutralizing single-domain V[SUB]L[/SUB] and an RNA hydrolyzing scFv
Phuong Thi Hoang[SUP] 1 2 [/SUP], Quynh Xuan Thi Luong[SUP] 1 [/SUP], Ramadhani Qurrota Ayun[SUP] 1 [/SUP], Yongjun Lee[SUP] 1 [/SUP], Kwang-Ji Oh[SUP] 1 2 [/SUP], Taehyun Kim[SUP] 2 [/SUP], Taek-Kyun Lee[SUP] 3 [/SUP], Sukchan Lee[SUP] 1 [/SUP]
Affiliations
- PMID: 38706966
- PMCID: PMC11066198
- DOI: 10.3389/fmicb.2024.1355599
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.
Keywords: 3D8 scFv; bio-panning; influenza virus; neutralizing antibodies; synergistic effect.