Even though Crimean-Congo Hemorrhagic Fever virus (CCHFV) is
a very old and well-recognized disease, little effort has been put to eradicate
either the disease or its symptoms. Besides ribavirin, T-705 has proven
historically reliable in reducing CCHF viremia and has been found to be the
most efficacious drug from a cohort of similar agents when used against a variety
of CCHFV strains.
Recently, a screen of candidate nucleoside analog compounds
identified 2′-deoxy-2′-fluorocytidine with increased activity in CCHFV compared
to ribavirin and T-705and showed antiviral activity against several
unrelated Bunyaviruses. Additionally, two repurposed FDA molecules
chloroquine and chlorpromazine showed direct activity against CCHFV. However,
there are practically no marketed alternatives available so far.
In a study published last month in Nature, researchers investigate CCHFV-RdRp, a critical mechanisms in the virus life cycle, which involves replication/transcription of vRNA in the cytoplasm of infected cell and an important target against CCHFV.
Because of the unavailability of CCHFV-RdRp crystal
structure in the protein database, an extensive approach to model CCHFV-RdRp
was undertaken to further identify potential anti-CCHFV compounds using
integrated computational methods. The in silico methods
provide a direct and scientifically well-funded basis to guide in vitro methods
for antiviral drug discovery.
The reported strategy is cost and time efficient, starting
from an extensively refined homology model of CCHFV RdRp as a potential
druggable target, followed by step-wise pharmacophore-based virtual screening
and all-atom backbone molecular dynamics simulation of potential hits.
Read the full paper at Nature.