# Soluble CD4 inhibits Ebola virus infection by targeting endosomal receptor-binding site

## TL;DR

Soluble CD4 and related compounds can block Ebola virus infection by targeting a key receptor site, similar to how they inhibit HIV.

## Contribution

Discovery that soluble CD4 and CD4-mimetics inhibit Ebola virus by targeting the NPC1 receptor binding site.

## Key findings

- Soluble CD4 inhibits Ebola virus infection by blocking the NPC1 receptor binding site.
- CD4-mimetic compounds also inhibit Ebola virus by targeting the same receptor site.
- The study reveals similarities in receptor binding mechanisms between HIV and Ebola viruses.

## Abstract

Human CD4 (cluster of differentiation 4) is well known as the primary receptor for human immunodeficiency virus (HIV) entry into the cells. The virus binds to CD4 molecules to induce a conformational change in the viral glycoprotein (GP) gp120, which exposes the co-receptor binding site for coreceptors CCR5 or CXCR4. The co-receptor binding then leads to membrane fusion for viral entry. Since the CD4 molecule has a high affinity for gp120, soluble CD4 (sCD4) and CD4-mimetic small molecules (CD4mcs) have been extensively studied as potential inhibitors for HIV infection. Surprisingly, we have found that human sCD4 and some CD4mcs are able to inhibit Ebola virus (EBOV) infection. Evidence is provided that the compounds block viral entry by targeting the GP binding site for the endosomal receptor Niemann-Pick C1 (NPC1). This finding reveals virus-receptor binding similarities between two remote viruses (HIV and EBOV) and suggests new possibilities for EBOV entry inhibitors.

•Soluble CD4 (sCD4) inhibits Ebola virus infection•CD4-mimetic small compounds (CD4mcs) inhibit Ebola virus infection•sCD4 and CD4mcs bind to NPC1 receptor binding site (RBS)•sCD4 and CD4mcs inhibit EBOV infection by targeting NPC1 RBS

Soluble CD4 (sCD4) inhibits Ebola virus infection

CD4-mimetic small compounds (CD4mcs) inhibit Ebola virus infection

sCD4 and CD4mcs bind to NPC1 receptor binding site (RBS)

sCD4 and CD4mcs inhibit EBOV infection by targeting NPC1 RBS

Biological sciences; Immunology; Microbiology; Natural sciences; Virology