A large
number of Food and Drug Administration (FDA)-approved drugs
have been found to inhibit the cell entry of Ebola virus (EBOV). However,
since these drugs have various primary pharmacological targets, their
mechanisms of action against EBOV remain largely unknown. We have
previously shown that six FDA-approved drugs inhibit EBOV infection
by interacting with and destabilizing the viral glycoprotein (GP).
Here we show that antidepressants imipramine and clomipramine and
antipsychotic drug thioridazine also directly interact with EBOV GP
and determine the mode of interaction by crystallographic analysis
of the complexes. The compounds bind within the same pocket as observed
for other, chemically divergent complexes but with different binding
modes. These details should be of value for the development of potent
EBOV inhibitors
