Anti-Chikungunya Virus Monoclonal Antibody That Inhibits Viral Fusion and Release
Uranan Tumkosit, Uamporn Siripanyaphinyo, Naokazu Takeda, Motonori Tsuji, Yusuke Maeda, Kriangsak Ruchusatsawat, Tatsuo Shioda, Hiroto Mizushima, Prukswan Chetanachan, Pattara Wongjaroen, Yoshiharu Matsuura, Masashi Tatsumi, Atsushi Tanaka
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.