Anti-Chikungunya Virus Monoclonal Antibody That Inhibits Viral Fusion and Release

Author:

Tumkosit Uranan1,Siripanyaphinyo Uamporn1,Takeda Naokazu2,Tsuji Motonori3,Maeda Yusuke2,Ruchusatsawat Kriangsak4,Shioda Tatsuo2,Mizushima Hiroto12,Chetanachan Prukswan4,Wongjaroen Pattara4,Matsuura Yoshiharu2,Tatsumi Masashi12,Tanaka Atsushi12ORCID

Affiliation:

1. Thailand-Japan Research Collaboration Center on Emerging and Re-emerging Infections (RCC-ERI), Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand

2. Research Institute for Microbial Diseases (RIMD), Osaka University, Suita, Osaka, Japan

3. Institute of Molecular Function, Misato, Saitama, Japan

4. National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand

Abstract

Recent outbreaks of chikungunya fever have increased its clinical importance. Neither a specific antiviral drug nor a commercial vaccine for CHIKV infection are available. Here, we show a detailed model of the docking between the envelope glycoprotein of CHIKV and our unique anti-CHIKV-neutralizing monoclonal antibody (CHE19), which inhibits CHIKV membrane fusion and virion release from CHIKV-infected cells. Homology modeling of the neutralizing antibody CHE19 and protein-protein docking analysis of the CHIKV envelope glycoprotein and CHE19 suggested that CHE19 inhibits the viral membrane fusion by stabilizing the E2-E1 heterodimer and inhibits virion release by facilitating the formation of virus aggregation due to the connecting virions, and these predictions were confirmed by experiments. Sequence information of CHE19 and the CHIKV envelope glycoprotein and their docking model will contribute to future development of an effective prophylactic and therapeutic agent.

Funder

Japan Agency for Medical Research and Development

MEXT | Japan Society for the Promotion of Science

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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