Intranasal Administration of Maleic Anhydride-Modified Human Serum Albumin for Pre-Exposure Prophylaxis of Respiratory Syncytial Virus Infection
Respiratory syncytial virus (RSV) is the leading cause of pediatric viral respiratory tract infections. Neither vaccine nor effective antiviral therapy is available to prevent and treat RSV infection. Palivizumab, a humanized monoclonal antibody, is the only product approved to prevent serious RSV i...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-02-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/7/2/798 |
| _version_ | 1818140744937897984 |
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| author | Zhiwu Sun Qian Wang Ran Jia Shuai Xia Yuan Li Qi Liu Wei Xu Jin Xu Lanying Du Lu Lu Shibo Jiang |
| author_facet | Zhiwu Sun Qian Wang Ran Jia Shuai Xia Yuan Li Qi Liu Wei Xu Jin Xu Lanying Du Lu Lu Shibo Jiang |
| author_sort | Zhiwu Sun |
| collection | DOAJ |
| description | Respiratory syncytial virus (RSV) is the leading cause of pediatric viral respiratory tract infections. Neither vaccine nor effective antiviral therapy is available to prevent and treat RSV infection. Palivizumab, a humanized monoclonal antibody, is the only product approved to prevent serious RSV infection, but its high cost is prohibitive in low-income countries. Here, we aimed to identify an effective, safe, and affordable antiviral agent for pre-exposure prophylaxis (PrEP) of RSV infection in children at high risk. We found that maleic anhydride (ML)-modified human serum albumin (HSA), designated ML-HSA, exhibited potent antiviral activity against RSV and that the percentages of the modified lysines and arginies in ML- are correlated with such anti-RSV activity. ML-HSA inhibited RSV entry and replication by interacting with viral G protein and blocking RSV attachment to the target cells, while ML-HAS neither bound to F protein, nor inhibited F protein-mediated membrane fusion. Intranasal administration of ML-HSA before RSV infection resulted in significant decrease of the viral titers in the lungs of mice. ML-HSA shows promise for further development into an effective, safe, affordable, and easy-to-use intranasal regimen for pre-exposure prophylaxis of RSV infection in children at high risk in both low- and high-income countries. |
| first_indexed | 2024-12-11T10:48:52Z |
| format | Article |
| id | doaj.art-ce2b8c63a50d491db375c43d2ffa8c14 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-11T10:48:52Z |
| publishDate | 2015-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-ce2b8c63a50d491db375c43d2ffa8c142022-12-22T01:10:24ZengMDPI AGViruses1999-49152015-02-017279881910.3390/v7020798v7020798Intranasal Administration of Maleic Anhydride-Modified Human Serum Albumin for Pre-Exposure Prophylaxis of Respiratory Syncytial Virus InfectionZhiwu Sun0Qian Wang1Ran Jia2Shuai Xia3Yuan Li4Qi Liu5Wei Xu6Jin Xu7Lanying Du8Lu Lu9Shibo Jiang10Key Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, ChinaKey Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, ChinaLaboratory Medicine Center, Pediatric Institute, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, ChinaKey Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, ChinaKey Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, ChinaKey Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, ChinaKey Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, ChinaLaboratory Medicine Center, Pediatric Institute, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, ChinaLindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USAKey Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, ChinaKey Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, ChinaRespiratory syncytial virus (RSV) is the leading cause of pediatric viral respiratory tract infections. Neither vaccine nor effective antiviral therapy is available to prevent and treat RSV infection. Palivizumab, a humanized monoclonal antibody, is the only product approved to prevent serious RSV infection, but its high cost is prohibitive in low-income countries. Here, we aimed to identify an effective, safe, and affordable antiviral agent for pre-exposure prophylaxis (PrEP) of RSV infection in children at high risk. We found that maleic anhydride (ML)-modified human serum albumin (HSA), designated ML-HSA, exhibited potent antiviral activity against RSV and that the percentages of the modified lysines and arginies in ML- are correlated with such anti-RSV activity. ML-HSA inhibited RSV entry and replication by interacting with viral G protein and blocking RSV attachment to the target cells, while ML-HAS neither bound to F protein, nor inhibited F protein-mediated membrane fusion. Intranasal administration of ML-HSA before RSV infection resulted in significant decrease of the viral titers in the lungs of mice. ML-HSA shows promise for further development into an effective, safe, affordable, and easy-to-use intranasal regimen for pre-exposure prophylaxis of RSV infection in children at high risk in both low- and high-income countries.http://www.mdpi.com/1999-4915/7/2/798human serum albumin (HSA)pre-exposure prophylaxis (PrEP)respiratory syncytial virus (RSV)entry inhibitorantiviral |
| spellingShingle | Zhiwu Sun Qian Wang Ran Jia Shuai Xia Yuan Li Qi Liu Wei Xu Jin Xu Lanying Du Lu Lu Shibo Jiang Intranasal Administration of Maleic Anhydride-Modified Human Serum Albumin for Pre-Exposure Prophylaxis of Respiratory Syncytial Virus Infection Viruses human serum albumin (HSA) pre-exposure prophylaxis (PrEP) respiratory syncytial virus (RSV) entry inhibitor antiviral |
| title | Intranasal Administration of Maleic Anhydride-Modified Human Serum Albumin for Pre-Exposure Prophylaxis of Respiratory Syncytial Virus Infection |
| title_full | Intranasal Administration of Maleic Anhydride-Modified Human Serum Albumin for Pre-Exposure Prophylaxis of Respiratory Syncytial Virus Infection |
| title_fullStr | Intranasal Administration of Maleic Anhydride-Modified Human Serum Albumin for Pre-Exposure Prophylaxis of Respiratory Syncytial Virus Infection |
| title_full_unstemmed | Intranasal Administration of Maleic Anhydride-Modified Human Serum Albumin for Pre-Exposure Prophylaxis of Respiratory Syncytial Virus Infection |
| title_short | Intranasal Administration of Maleic Anhydride-Modified Human Serum Albumin for Pre-Exposure Prophylaxis of Respiratory Syncytial Virus Infection |
| title_sort | intranasal administration of maleic anhydride modified human serum albumin for pre exposure prophylaxis of respiratory syncytial virus infection |
| topic | human serum albumin (HSA) pre-exposure prophylaxis (PrEP) respiratory syncytial virus (RSV) entry inhibitor antiviral |
| url | http://www.mdpi.com/1999-4915/7/2/798 |
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