Mode of inactivation of arenaviruses by disulfide-based compounds

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

Villa Carlos Paz, Córdoba, Argentina

Congreso; XXXVII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2001

<!-- /* 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:595.3pt 841.9pt; margin:70.9pt 3.0cm 70.9pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Previous studies have identified 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. 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. Then, 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. Thus, these compounds inactivate virion infectivity generating particles, which enter the host cell but are unable to complete the viral biosynthetic pathway process.