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Crimean Congo Countermeasures: Researchers Investigate CCHFV-RDRp

Crimean-Congo hemorrhagic fever viral particles (orange). Credit NIAID, modified.

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.

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