Concentration Dependent Inhibitory Effect of a Nucleoside-based Analog Against Human Herpesvirus-6 Replication (P6.304)

Human herpesvirus-6 (HHV-6) is associated with a number neurological disorders including multiple sclerosis (MS). To test the hypothesis of HHV-6 association in MS, certain approved human herpesvirus therapies have been investigated for treatment against HHV-6 in MS patients. However, antiviral therapies specific for HHV-6 do not exist. Therefore, antivirals that primarily targert other β-herpesviruses such as human cytomegalovirus (HCMV) are often used in these trials but with minimal efficacy. Recently, a subset of nucleoside-based analogs was reported with improved efficacy against herpesviruses. Therefore, our goal is to further investigate the potential antiviral properties of the cyclopropavir derivative, 2,2-bis-hydroxymethyl-cyclopropavir (ZSM-I-62), against HHV-6. In our studies, ZSM-I-62 was investigated in vitro against the HHV-6A (strain U1101) and HHV-6B (strain Z29) variants with HSB-2 and SUPT-1 T-cell lines, respectively. The proviral loads within the supernatant and cell lysates were detected with real-time Taqman PCR. For HHV-6B, ZSM-I-62 inhibited viral replication relative to DMSO in both the supernatant and cell lysate by approximately 3 to 4 logs over a period of seven days. A concentration dependent inhibitory effect was also observed for serial dilutions (1:10) of ZSM-I-62. When infected cells were left untreated for three days, the addition of ZSM-I-62 inhibited viral replication starting from time of addition and throughout the remaining seven-...
Source: Neurology - Category: Neurology Authors: Tags: HTLV and Other Viral Infections Source Type: research