A novel MARV glycoprotein-specific antibody with potentials of broad-spectrum neutralization to filovirus

Zhang, Y.; Zhang, M.; Wu, H.; Wang, X.; Zheng, H.; Feng, J.; Wang, J.; Luo, L.; Xiao, H.; Qiao, C.; Li, X.; Zheng, Y.; Huang, W. J.; Wang, Y.; Shi, Y.; Chen, G.

doi:10.1101/2023.09.17.558100

bioRxiv · 10.1101/2023.09.17.558100

A novel MARV glycoprotein-specific antibody with potentials of broad-spectrum neutralization to filovirus

Zhang, Y.·Zhang, M.·Wu, H.·Wang, X.·Zheng, H.·Feng, J.·Wang, J.·Luo, L.·Xiao, H.·Qiao, C.·Li, X.·Zheng, Y.·Huang, W. J.·Wang, Y.·Shi, Y.·Chen, G.

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Abstract

Marburg virus (MARV) is one of the filovirus species that cause deadly hemorrhagic fever in humans, with mortality rates up to 90%. Neutralizing antibodies represent ideal candidates to prevent or treat virus disease. However, no antibody has been approved for MARV treatment to date. In this study, we identified a novel human antibody named AF-03 that targeted MARV glycoprotein (GP). AF-03 possessed a high binding affinity to MARV GP and showed neutralizing and protective activities against the pseudotyped MARV in vitro and in vivo. Epitope identification, including molecular docking and experiment-based analysis of mutated species, revealed that AF-03 recognized the Niemann-Pick C1 (NPC1) binding domain within GP1. Interestingly, we found the neutralizing activity of AF-03 to pseudotyped Ebola viruses (EBOV, SUDV, and BDBV) harboring cleaved GP instead of full-length GP. Furthermore, NPC2-fused AF-03 exhibited neutralizing activity to several filovirus species and EBOV mutants via binding to CI-MPR. In conclusion, this work demonstrates that AF-03 represents a promising therapeutic cargo for filovirus-caused disease.

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Zhang, Y., Zhang, M., Wu, H., Wang, X., Zheng, H., Feng, J., Wang, J., Luo, L., Xiao, H., Qiao, C., Li, X., Zheng, Y., Huang, W. J., Wang, Y., Shi, Y., Chen, G.. 2023-09-17. A novel MARV glycoprotein-specific antibody with potentials of broad-spectrum neutralization to filovirus. https://doi.org/10.1101/2023.09.17.558100

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