{Reference Type}: Journal Article
{Title}: A novel MARV glycoprotein-specific antibody with potentials of broad-spectrum neutralization to filovirus.
{Author}: 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;Wang Y;Wang Y;Shi Y;Feng J;Chen G;
{Journal}: Elife
{Volume}: 12
{Issue}: 0
{Year}: 2024 Mar 25
{Factor}: 8.713
{DOI}: 10.7554/eLife.91181
{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.