Targeting SUMO Modification of the Non-Structural Protein 5 of Zika Virus as a Host-Targeting Antiviral Strategy
AbstractPost-translational modifications of host or viral proteins are key strategies exploited by viruses to support virus replication and counteract host immune response. SUMOylation is a post-translational modification process mediated by a family of ubiquitin-like proteins called small ubiquitin-like modifier (SUMO) proteins. Multiple sequence alignment of 78 representative flaviviruses showed that most (72/78, 92.3%) have a putative SUMO-interacting motif (SIM) at their non-structural 5 (NS5) protein’s N-terminal domain. The putative SIM was highly conserved among 414 pre-epidemic and epidemic Zika virus (ZIKV) strains, with all of them having a putative SIM core amino acid sequence of VIDL (327/414, 79.0%) or VVDL (87/414, 21.0%). Molecular docking predicted that the hydrophobic SIM core residues bind to the β2 strand of the SUMO-1 protein, and the acidic residues flanking the core strengthen the binding through interactions with the basic surface of the SUMO protein. The SUMO inhibitor 2-D08 significantly reduced replication of flaviviruses and protected cells against ZIKV-induced cytopathic effects in vitro. A SIM-mutated ZIKV NS5 failed to efficiently suppress type I interferon signaling. Overall, these findings may suggest SUMO modification of the viral NS5 protein to be an evolutionarily conserved post-translational modification process among flaviviruses to enhance virus replication and suppress host antiviral response. View Full-Text
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Zhu, Z.; Chu, H.; Wen, L.; Yuan, S.; Chik, K. .-H.; Yuen, T. .-T.; Yip, C. .-Y.; Wang, D.; Zhou, J.; Yin, F.; Jin, D.-Y.; Kok, K.-H.; Yuen, K.-Y.; Chan, J. .-W. Targeting SUMO Modification of the Non-Structural Protein 5 of Zika Virus as a Host-Targeting Antiviral Strategy. Int. J. Mol. Sci. 2019, 20, 392.
Zhu Z, Chu H, Wen L, Yuan S, Chik K -H, Yuen T -T, Yip C -Y, Wang D, Zhou J, Yin F, Jin D-Y, Kok K-H, Yuen K-Y, Chan J -W. Targeting SUMO Modification of the Non-Structural Protein 5 of Zika Virus as a Host-Targeting Antiviral Strategy. International Journal of Molecular Sciences. 2019; 20(2):392.Chicago/Turabian Style
Zhu, Zheng; Chu, Hin; Wen, Lei; Yuan, Shuofeng; Chik, Kenn .-H.; Yuen, Terrence .-T.; Yip, Cyril .-Y.; Wang, Dong; Zhou, Jie; Yin, Feifei; Jin, Dong-Yan; Kok, Kin-Hang; Yuen, Kwok-Yung; Chan, Jasper .-W. 2019. "Targeting SUMO Modification of the Non-Structural Protein 5 of Zika Virus as a Host-Targeting Antiviral Strategy." Int. J. Mol. Sci. 20, no. 2: 392.
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