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Inhibition of nuclear transport of
pathogenic kariophilic proteins:
Many pathogenic agents such as viruses use the cellular nuclear
import pathway in-order to transport viral proteins into the cell nucleus. These
viral proteins contain a unique Nuclear Localization Signals (NLS’s), which are
able to mediate interactions of the viral proteins and importins and thus be
transported to the nucleus. Since there is no consensus NLS sequence the viral
NLS is a good target for development of inhibitors.
We are screening for peptide inhibitors, which will block
specifically the nuclear import of human HIV-1 and the plant Gemini virus
kariophilic proteins using two main concepts.
a. In collaboration with Prof. Chaim Gilon we are synthesizing
backbone cyclic peptides, which mimic the NLS sequence and are able to block the
viral protein nuclear trans location.

Cyclic HIV-1 Rev peptide
mimicking the Rev Argenin Rich Motif (ARM).
From:Hariton-Gazal,
et al Biochemistry 2005, 44, 11555-11566.
b. Using different in-vivo and in-vitro screening methods we are
searching for short peptides which will bind specifically to viral NLS sequences
and thus block viral protein and nucleic acid nuclear
import.

Inhibition of nuclear up-take of the HIV VprN peptide with a
fragment obtained using a phage display
library
From: Krichevsky, A. et al.
Virology 2003, 305,
77–92.
The same approach is used in
collaboration with Prof. Vitaly Citovsky to develop peptides that will
specifically bind to the NLSs of the Agrobacterium VirE2 and to that of the
TYLCV coat protein. This is in order to develop peptides that wiil inhibit
infection of plants by Agrobacteriun and by TYLCV (The tomato yellow curl leaf
virus).
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