Filovirus gp Specific Neutra™ Antibody Products

Filoviruses are negative-sense, single-stranded RNA viruses classified in the family Filoviridae, of which Ebola and Marburg viruses (EBOV and MARV) are commonly known. They are highly pathogenic and primarily transmitted to humans and/or nonhuman primates through direct contact with infected bodily fluids. Filovirus outbreaks, notably Ebola, cause severe hemorrhagic fever and are characterized by high fatality rates. The glycoprotein (gp) of filoviruses is the only particle surface protein and helps filoviruses attach to and enter cells. The gp protein also triggers immune responses, including inflammation, and can be a target for therapeutic interventions. Its function is essential for both viral infectivity and pathogenesis.

Structure of Filovirus gp

The filovirus GP is a trimeric, class I fusion protein projecting as spikes from the viral envelope. Heavily glycosylated, GP is essential for viral entry. GP comprises receptor-binding GP1 and membrane-fusion GP2 subunits, produced via proteolytic cleavage of a single precursor and remained linked by a disulfide bond. GP1 has a receptor-binding domain, a glycan cap and a mucin-like domain (MLD), while GP2 contains a fusion peptide responsible for membrane fusion. Upon cellular entry, GP1 is cleaved and shed, triggering dramatic GP2 conformational changes. This exposes the fusion loop, inserting into the host cell membrane. GP2 then refolds into a six-helix bundle, driving membrane merger and viral entry. These structural rearrangements are essential for infection.

Fig. 1 EBOV and MARV genome structures, and EBOV GP structure.¹

gp-Mediated Viral Attachment and Entry

Filovirus gp mediates viral attachment and entry into host cells through a multistep process. After entering the endosome, GP is processed by host cathepsins, removing the glycan cap and MLD, which allows GP to bind to NPC1 to specific host cell receptors, such as the NPC1 protein, which is crucial for viral recognition. After attachment, the virus is internalized via endocytosis, where the acidic environment inside the endosome induces conformational changes in the GP2 subunit. This triggers the exposure of the fusion peptide, allowing the viral and endosomal membranes to fuse. The fusion event releases the viral RNA into the host cell cytoplasm, triggering infection. The GP-mediated entry process is essential for viral infectivity and is targeted by potential antiviral therapies aimed at disrupting the fusion process or blocking receptor binding.

Filovirus gp Neutralizing Antibodies

Antibodies targeting filovirus GP are the focus of antiviral therapies and vaccines. Neutralizing antibodies bind to the GP, blocking viral attachment to host cell receptors and preventing membrane fusion. This inhibits the virus's ability to enter host cells and reduces infection. Several neutralizing antibodies have been confirmed in animal models infected with filoviruses and through clinical trials. For example, monoclonal antibodies, a cocktail targeting GP, have shown effectiveness against EBOV. Additionally, a human antibody that targets the MARV GP has been demonstrated to have neutralizing and protective activities against MARV in vitro and in vivo. These antibodies are designed to neutralize viral entry by preventing the conformational changes in GP required for membrane fusion, offering promising therapeutic and prophylactic applications in treating filovirus infections.

Fig. 2 Summary of neutralizing antibodies (pink boxes) and non-neutralizing antibodies against Filovirus gp.¹

Based on rich experience in the field of antibody development, Creative Biolabs provides global customers with quality anti-Filovirus gp neutralizing antibodies to accelerate your research progress.

REFERENCE

1. Hargreaves, Alexander, et al. "Filovirus neutralising antibodies: mechanisms of action and therapeutic application." Pathogens 10.9 (2021): 1201. Distributed under Open Access license CC BY 4.0, without modification.