Abstract
Abstract: :
Purpose: Adenovirus, one of the most common external ocular viral infections worldwide, is associated with significant patient morbidity and visual disturbances that can last years. Currently, there is no topical antiviral treatment available for adenovirus. We evaluated a number of transition metal complexes (CTC compounds) which exhibit potent antiviral activity and whose mode of action differs from that of the currently available antiviral nucleoside analogs. Prior research has identified a leading CTC compound (CTC-96) which has in vitro and in vivo HSV antiviral efficacy. Methods: Previous studies have shown that Adenovirus type 5 (Ad5) has the ability to replicate in rabbits and rabbit cells. The biological anti-adenovirus activity of newly synthesized CTC compounds was evaluated by standardized cell culture viral inactivation (CTC-virus neutralization), virucidal (CTC-virus neutralization with post-neutralization CTC exposure) and antiviral plaque reduction (effect of CTC compounds on previously adsorbed virus) assays on HeLa (human cervical carcinoma), A549 (human lung carcinoma) and SIRC CRL-60 (rabbit corneal) cells. Results: Viral Inactivation, Virucidal and Antiviral Assays demonstrated CTC-96 to be effective against Ad5. In all cases, peak efficacy was observed in concentrations ≥50 µg/ml, while lower concentrations showed decreasing dose-responsiveness. Greater viral replication/yield and antiviral activity was observed in HeLa ≷A549 ≷ SIRC. Conclusion: CTC-96 demonstrated anti-adenoviral (Ad5) activity in tissue culture with human (HeLa, A549) and rabbit (SIRC) cell lines. Animal studies will need to be done to determine clinical significance.
Keywords: 307 adenovirus • 322 antiviral drugs • 372 cornea: epithelium