We found that the cholesterol-conjugated C-peptides were potent inhibitors of Ebola virus glycoprotein (GP -mediated cell entry (∼103-fold reduction in infection at 40 μM).
These results, again, suggest that the E2 glycoprotein plays critical role for neurovirulence of the SINV in suckling mouse, which is correlated to HS-mediated cell entry.
115 Subsequent biological characterization of these isolates demonstrated CD8-mediated cell entry without the requirement for any known chemokine coreceptor.
Although the mechanism of inhibition appears to be unspecific (the peptides also showed activity against the vesicular stomatitis virus glycoprotein G), the cholesterol-conjugated C-peptides were potent inhibitors of EBOV glycoprotein-mediated cell entry.
Beyond innate immunity and receptor-mediated cell entry, there are exciting new results from comparative studies of virus host interactions across the family tree of viruses that identify new cellular pathways that can be hijacked by viruses or that suppress their replication.
223 Ferrer and colleagues used a combinatorial chemical library to find elements that, when covalently attached to a peptide derived from the outer layer α-helix, could inhibit gp-41-mediated HIV-1 cell entry.
This differs to the mechanism evolved by Salmonella typhimurium, in which two distinct T3SS and effector cohorts individually trigger bacterial-mediated endocytosis during cell entry and manipulate host membrane trafficking to promote intracellular bacterial replication within the Salmonella-containing vacuole (Srikanth et al., 2011).
p27Kip1 is an inhibitor of a broad spectrum of cyclin-dependent kinases (CDKs), and the loss of a single p27Kip1 allele is thereby sufficient to increase tumor incidence via CDK-mediated cell cycle entry.
Overexpression of PHB in LNCaP cells inhibited androgen-mediated cell cycle entry, cell growth and gene expression, both in cell culture and in tumour xenografts.
Preventing cyclin C-mediated cell cycle entry or simultaneous blocking of CDK4 and CDK6, both important during G1 progression (Fig. 1), augmented DNA damage upon hydrogen peroxide exposure [ 83, 95].
