Engineered Human Monoclonal scFv to Receptor Binding Domain of <i>Ebolavirus</i>

• Main Authors: Jaslan Densumite, Siratcha Phanthong, Watee Seesuay, Nitat Sookrung, Urai Chaisri, Wanpen Chaicumpa
• Format: Article
• Language: English
• Published: MDPI AG 2021-05-01
• Series: Vaccines
• Subjects: human single-chain antibodies (HuscFvs); cell-penetrating antibodies; <i>Ebolavirus</i>; <i>Ebolavirus</i>-like particles; Glycoprotein (GP); Cleaved GP (GPcl)
• Online Access: https://www.mdpi.com/2076-393X/9/5/457

(1) Background: <i>Ebolavirus</i> (EBOV) poses as a significant threat for human health by frequently causing epidemics of the highly contagious Ebola virus disease (EVD). EBOV glycoprotein (GP), as a sole surface glycoprotein, needs to be cleaved in endosomes to fully expose a receptor-binding domain (RBD) containing a receptor-binding site (RBS) for receptor binding and genome entry into cytoplasm for replication. RBDs are highly conserved among EBOV species, so they are an attractive target for broadly effective anti-EBOV drug development. (2) Methods: Phage display technology was used as a tool to isolate human single-chain antibodies (HuscFv) that bind to recombinant RBDs from a human scFv (HuscFv) phage display library. The RBD-bound HuscFvs were fused with cell-penetrating peptide (CPP), and cell-penetrating antibodies (transbodies) were made, produced from the phage-infected <i>E. coli</i> clones and characterized. (3) Results: Among the HuscFvs obtained from phage-infected <i>E. coli</i> clones, HuscFvs of three clones, HuscFv4, HuscFv11, and HuscFv14, the non-cell-penetrable or cell-penetrable HuscFv4 effectively neutralized cellular entry of EBOV-like particles (VLPs). While all HuscFvs were found to bind cleaved GP (GPcl), their presumptive binding sites were markedly different, as determined by molecular docking. (4) Conclusions: The HuscFv4 could be a promising therapeutic agent against EBOV infection.