Chemically Modified Human Serum Albumin Potently Blocks Entry of Ebola Pseudoviruses and Viruslike Particles.
Ebola virus (EBOV), the causative pathogen of the deadly Ebola virus disease (EVD), can be transmitted via contact with EVD patients, including sexual contact with EVD survivors. At present, no licensed vaccine or therapeutic is available. In this study, we compared eight anhydride-modified proteins for their entry-inhibitory activity against the pseudovirus (PsV) carrying the envelope glycoprotein (GP) of the EBOV Zaire or Sudan species (Zaire PsV and Sudan PsV, respectively). We found that 3-hydroxyphthalic anhydride-modified human serum albumin (HP-HSA) was the most effective in inhibiting the entry of both Zaire PsV and Sudan PsV, with the 50% effective concentration being at the nanomolar level and with HP-HSA being more potent than EBOV-neutralizing antibody MIL77-2 (4G7, a component antibody of the ZMapp drug cocktail). The combination of HP-HSA and MIL77-2 exhibited a synergistic effect. HP-HSA had no obviousin vitroorin vivotoxicity. The EBOV PsV entry-inhibitory activity of HP-HSA remained intact after storage at 45°C for 8 weeks, suggesting that HP-HSA has the potential for worldwide use, including tropical regions in African countries, as either a therapeutic to treat EBOV infection or a prophylactic microbicide to prevent the sexual transmission of EBOV.
Key Lab of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Haoyang
H
Li
Key Lab of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Fei
F
Yu
Key Lab of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Shuai
S
Xia
Key Lab of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Yufeng
Y
Yu
Key Lab of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Qian
Q
Wang
Institute of Basic Medical Sciences, Beijing, China.
Ming
M
Lv
Shanghai Information Center for Life Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Yan
Y
Wang
Key Lab of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China shibojiang@fudan.edu.cn lul@fudan.edu.cn.|Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA.
Shibo
S
Jiang
Key Lab of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China shibojiang@fudan.edu.cn lul@fudan.edu.cn.
Lu
L
Lu
D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D000914:Antibodies, Viral / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D029043:Ebolavirus / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D015870:Gene Expression; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control; D006801:Humans; D008958:Models, Molecular; D018716:Molecular Mimicry; D010796:Phthalic Anhydrides / Q000737:chemistry / Q000494:pharmacology*; D011322:Primary Prevention; D012709:Serum Albumin / Q000737:chemistry / Q000494:pharmacology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D053586:Virus Internalization / Q000187:drug effects*
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000998:Antiviral Agents; D004338:Drug Combinations; D010796:Phthalic Anhydrides; D012709:Serum Albumin; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus; C478070:3-hydroxyphthalic anhydride
Ebola virus; anhydride-modified protein; microbicide; sexual transmission; therapeutic drug; viral entry