title: Intranasal administration of maleic anhydride-modified human serum albumin for pre-exposure prophylaxis of respiratory syncytial virus infection.
abstract: 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.
authors.affiliation: Key Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China. haoyunzhiwu@163.com.
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Key Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China. miaqian@foxmail.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Laboratory Medicine Center, Pediatric Institute, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. goodbye_sea@126.com.
authors.forename: Ran
authors.initials: R
authors.lastname: Jia
authors.affiliation: Key Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China. 928958768@qq.com.
authors.forename: Shuai
authors.initials: S
authors.lastname: Xia
authors.affiliation: Key Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China. liyuan.mic@gmail.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China. qiliu@aliyun.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Key Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China. xuwei0576@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Laboratory Medicine Center, Pediatric Institute, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. jinxu_125@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA. lanydu2007@gmail.com.
authors.forename: Lanying
authors.initials: L
authors.lastname: Du
authors.affiliation: Key Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China. lul@fudan.edu.cn.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: Key Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China. shibojiang@fudan.edu.cn.|Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA. shibojiang@fudan.edu.cn.
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008299:Maleic Anhydrides / Q000737:chemistry; D051379:Mice; D008826:Microbial Sensitivity Tests; D065129:Pre-Exposure Prophylaxis; D011485:Protein Binding; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D018113:Respiratory Syncytial Virus, Human / Q000187:drug effects*; D012709:Serum Albumin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D008299:Maleic Anhydrides; D012709:Serum Albumin; D014759:Viral Envelope Proteins