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Figure 2 | Infectious Diseases of Poverty

Figure 2

From: Possible FDA-approved drugs to treat Ebola virus infection

Figure 2

Model of the therapeutic mechanisms at the subcellular level: Drugs are shown with the stroke red color. EBOV, Ebola virus; L, viral RNA polymerase L protein. In addition to the viral surface glycoprotein (GP trimer), EBOV directs the production of large quantities of a truncated glycoprotein isoform (sGP dimer) that is secreted into the extracellular space. sGP can absorb anti-GP neutralizing antibodies (green ‘Y’) [9]. On the other hand, another antibody against glycosylated GP peptides is generated (purple ‘Y’), which enhances virus infection. The complement component C1q increases the likelihood of viral attachment to the cell surface [10,11]. Inhibition to GP glycans (dark-blue dot outside the GP protein) may reduce this antibody-dependent enhancement (ADE) ideally. Miglustat is a clinically-approved glycosidase inhibitor. Three derivates of Miglustat showed significant in-vitro antiviral activities against EBOV [23]. T-cell Ig and mucin domain 1 (TIM-1) and Niemann-Pick C1 (NPC1) are cellular receptors for EBOV [15,25]. The membrane fusion mediated by EBOV glycoproteins and viral escape from the vesicular compartment require the NPC1 protein [25]. Most NPC1 inhibitors are benzylpiperazine adamantane diamide derivates, non-FDA-approved drugs [26]. Recent studies showed that Clomiphene and Toremifene are novel NPC1 inhibitors and act as potential inhibitors of EBOV [27,28]. Viral VP24 protein inhibits nuclear import of the transcription factor STAT1, preventing interferon production [13]. Ouabain inhibits this process [14]. Two leukemia drugs Gleevec and Tasigna lower Ebola virus replication by inhibiting c-AbI1 tyrosine kinase, which is required for the release of Ebola virus particles [17].

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