Abstract
(1) Background: Ebolavirus (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 E. coli clones and characterized. (3) Results: Among the HuscFvs obtained from phage-infected E. coli 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.
Highlights
Ebolavirus (EBOV) is a highly contagious pathogen causing severe illness with rapid progression and high mortality rates, i.e., Ebolavirus disease (EVD) or Ebola hemorrhagic fever (EHF), which is endemic in the African territory [1]
Soluble human scFv (HuscFv) were produced from the huscfv-positive E. coli clones
The huscfvs of the recombinant RBD (rRBD)-bound HuscFv clones were subjected to DNA sequencing
Summary
Ebolavirus (EBOV) is a highly contagious pathogen causing severe illness with rapid progression and high mortality rates, i.e., Ebolavirus disease (EVD) or Ebola hemorrhagic fever (EHF), which is endemic in the African territory [1]. The EBOV RNA genome is about 18–19 kb in size and encodes seven proteins, including nucleoprotein (NP), which encases the genomic RNA; virion protein (VP) 35, which has polymerase co-factor activity and the ability to suppress the host’s innate immunity for immune evasion; VP40, which drives the progeny virus assembly and budding; glycoprotein (GP), which functions in host cell attachment and virus entry; transcription factor VP30, which forms complex with the L (polymerase) protein for protein synthesis and genome replication; VP24, which can inhibit interferon signaling; and L protein, which is the viral RNA-dependent RNA polymerase [4]. The six species differ in the disease severity that they cause; the Zaire ebolavirus causes the most severe form of EVD, while the Reston ebolavirus causes EVD in non-human primates and has not been known to cause human disease [6]. The GP1 which facilitates host cell attachment and receptor binding for cellular entry, consists of a glycan cap (GC), a heavily-glycosylated mucin-like domain (MLD), and a receptor-binding domain (RBD)
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