Host targeted antiviral (HTA): functional inhibitor compounds of scaffold protein RACK1 inhibit herpes simplex virus proliferation.

Host targeted antiviral (HTA): functional inhibitor compounds of scaffold protein RACK1 inhibit herpes simplex virus proliferation. Oncotarget. 2019 May 14;10(35):3209-3226 Authors: Ullah H, Hou W, Dakshanamurthy S, Tang Q Abstract Due to the small number of molecular targets in viruses and the rapid evolution of viral genes, it is very challenging to develop specific antiviral drugs. Viruses require host factors to translate their transcripts, and targeting the host factor(s) offers a unique opportunity to develop broad antiviral drugs. It is well documented that some viruses utilize a host protein, Receptor for Activated C Kinase 1 (RACK1), to translate their mRNAs using a viral mRNA secondary structure known as the Internal Ribosomal Entry Site (IRES). RACK1 is essential for the translation of many viruses including hepatitis C (HCV), polio, Drosophila C (DCV), Dengue, Cricket Paralysis (CrpV), and vaccinia viruses. In addition, HIV-1 and Herpes Simplex virus (HSV-1) are known to use IRES as well. Therefore, host RACK1 protein is an attractive target for developing broad antiviral drugs. Depletion of the host's RACK1 will potentially inhibit virus replication. This background study has led us to the development of novel antiviral therapeutics, such as RACK1 inhibitors. By utilizing the crystal structure of the RACK1A protein from the model plant Arabidopsis and using a structure based drug design method, dozens of small compounds were identified that c...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research

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