We recently described the synthesis and antiviral activity of the compounds 5-phenyl-3-(4-cyano-5-phenylisothiazol-3-yl) disulphanyl-4-isothiazole-carbonitrile and S-(4-cyano-5-phenylisothiazol-3-yl)- O-ethyl thiocarbonate, which were found to be effective against both HIV-1 (IIIB) and HIV-2 (ROD). We have now evaluated these compounds against both RNA and DNA viruses, obtaining high selectivity indexes for poliovirus 1 (SI: 223 and 828, respectively) and Echovirus 9 (SI: 334 and 200, respectively). In our previous studies, 3-methylthio-5-(4- OBn-phenyl)-4-isothiazolecarbo-nitrile was found to exhibit a broad spectrum of action against picornaviruses, we therefore selected this compound and S-(4-cyano-5-phenylisothiazol-3-yl)- O-ethyl thiocarbonate as the model for the synthesis of a new isothiazole derivative, S-[4-cyano-5-(4- OBn-phenyl)isothiazol-3-yl]- O-ethyl thiocarbonate. This compound was evaluated against picornaviruses, measles virus, HIV-1 (IIIB) and HIV-2 (ROD), and some DNA viruses (adenovirus type 2 and herpes simplex virus type 1). The compound was shown to be active against rhinoviruses 2, 39, 86 and 89, Coxsackie B1 and measles virus.
Adeno-Associated Viruses Can Induce Phosphorylation of eIF2α via PKR Activation, Which Can Be Overcome by Helper Adenovirus Type 5 Virus-Associated RNA