Inactivation of arenaviruses by disulfide-based compounds

E. B. DAMONTE; C. C. GARCÍA; NÉLIDA A. CANDURRA

Praga, República Checa

Conferencia; Fifteenth International Conference on Antiviral Research; 2002

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} p.MsoBodyText, li.MsoBodyText, div.MsoBodyText {margin-top:0cm; margin-right:134.6pt; margin-bottom:0cm; margin-left:0cm; margin-bottom:.0001pt; text-align:justify; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Previous studies have identified a series of known antiretroviral Zn finger compounds as effective inhibitors of arenavirus infection. The present report describes the inactivating effect of three such compounds on Junin (JUNV) and Tacaribe (TCRV) viruses. To assay the virucidal activity, a virus suspension was exposed for 1.5 h at 37ºC to various concentrations of compounds and dilute to determine residual infectivity by plaque formation. The aromatic disulfide NSC 20625 and the dithianes NSC 624151 and 624152, provided by the National Cancer Institute (USA), were potent virucidal agents. The inactivating concentration 50% of the compounds against both arenaviruses were calculated to be in the range 0.2-3.2 µM. The time course of virucidal activity showed that the inactivation started a few minutes after addition of the compound to the virus suspension and proceeded in a time-dependent manner. Arenavirus inactivation was also energy-dependent since a temperature higher than 30ºC was required to destroy virus infectivity. To gain some insight into the mechanism by which the compounds inactivate arenavirus, we tested the ability of drug-treated virus to perform several steps of the replication cycle. [35S]-labeled virions were incubated in the presence or absence of the compounds, and then the adsorption and internalization of treated or control virions to Vero cells was determined. Results showed that inactivated virus bound and entered the cell with the same efficacy as control virus. By contrast, the ability of the drug-treated virus to synthesize viral proteins was affected. No viral proteins were observed in cells infected with killed virus preparation whereas in cells infected with control virus the main viral proteins NP and GP, were detected. Thus, these compounds inactivate virion infectivity generating particles, which enter the host cell but are unable to complete the viral biosynthetic pathway process.