Antiviral properties of cobalt(III)-complexes

We have investigated the potential antiviral activity of three cobalt(III) compounds. Two compounds, Co(III)-cyclenmethylbenzoic acid and its methyl ester derivative, are based on the macrocyclic chelator, cyclen, and were synthesized in our laboratory. Both compounds have been shown to bind tightly to nucleic acids and to hydrolyze phosphodiester bonds. However, neither compound exhibited any significant antiviral activity in an in vitro model of Sindbis virus replication. In contrast, a third compound, Co(III)hexammine, significantly inhibited Sindbis virus replication in baby hamster kidney (BHK) cells in a dose and time-dependent manner. In plaque assays, the incubation of Co(III)hexammine with Sindbis virus resulted in a dose-dependent decrease in virus replication when measured at both 24 and 48-h post-infection. Over the concentration range of 0-5 mM Co(III)hexammine, the IC50 for the inhibition of viral replication was determined to be 0.10 +/- 0.04 mM at 48 It. Additionally, when BHK cell monolayers were pretreated with Co(III)hexammine for 6 It prior to Sindbis infection, optimal cellular morphology and plasma membrane integrity were observed Lit 0.6-1.2 mM Co(III)hexammine. Analysis by flow cytometry confirmed that Co(III)hexammine mediated a concomitant dose-dependent increase in BHK cell viability and a decrease in the percentage of Sindbis virus-infected cells (IC50 = 0.13 +/- 0.04 mM). Our findings demonstrate for the first time that Co(III)hexammine possesses potent antiviral activity. We discuss our findings within the context of the ability to further functionalize Co(III)hexammine to render it a highly specific antiviral therapeutic reagent. Published by Elsevier Ltd.