Evaluación de la actividad antiviral contra arenavirus de agentes inhibidores de proteínas Zn finger

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

Buenos Aires

Congreso; VIII Congreso Argentino de Microbiología; 1998

<!-- /* 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.MsoBodyText2, li.MsoBodyText2, div.MsoBodyText2 {margin:0cm; margin-bottom:.0001pt; text-align:justify; mso-pagination:widow-orphan; font-size:12.0pt; mso-bidi-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;} --> Arenaviruses such as Lassa virus, Junín virus and Machupo virus cause hemorrhagic fevers in human beings. The virions contain bisegmented single-stranded RNA genomes called S (small) and L  (large). Both fragments have ambisense  coding strategy and express five different products: a nucleocapsid protein (NP), an envelope glycoprotein precursor (GPC) that is processed into GP1 and GP2, an RNA polymerase (L) and an 11-kda protein (Z) with unknown function. The Z protein was the last to be described and contains a RING finger domain that uses conserved cysteines and a histidine to bind Zn. The conservation of the Zn–binding domain in the 11 kda–Z protein of several arenaviruses makes this protein an attractive target for antiviral therapy. Recent studies have identified a series of chemotypes that target the retroviral Zn finger motifs of HIV–1 p7 nucleocapsid  protein causing Zn ejection from the protein and inhibition of virus replication. In the present study, we evaluated selected retroviral Zn finger agents for their capacity to act as arenavirus inhibitors.