In Vitro and in Vivo Studies of Ribavirin Action on Brazilian Orthobunyavirus

Abstract

Oropouche, Caraparu, Guama, Guaroa, and Tacaiuma are viruses (genus Orthobunyavirus) that cause human febrile illnesses and encephalitis. The goal of this study was to evaluate the antiviral action of ribavirin on these orthobunyaviruses to achieve a therapeutical agent to treat the diseases caused by these viruses. In vitro results showed that ribavirin (50 microg/mL) had antiviral activity only on the Tacaiuma virus. Addition of guanosine in the culture reversed the antiviral effect of ribavirin on Tacaiuma virus, suggesting that ribavirin inhibited this virus by reducing the intra-cellular guanosine pool. Moreover, ribavirin was not an effective drug in vivo because it was unable to inhibit the death of the mice or virus replication in the brain. The results suggest that ribavirin has no antiviral activity on the Oropouche, Caraparu, Guama, Guaroa, or Tacaiuma viruses; consequently, ribavirin would not be a good therapeutical agent to treat these arboviruses.

In vitro and in vivo studies of the Interferon-alpha action on distinct Orthobunyavirus

“…In vitro antiviral evaluation was done with a plaque assay (Livonesi et al, 2006). Vero E6 cells were seeded in 24-well plates in MEM with 10% FBS, for 24 h at 37 • C and 5% CO 2 .…”

“…An antiviral therapy, if available, would be a very helpful intervention, reducing symptoms and disease period of OROV fever as well as of those febrile illnesses caused by other orthobunyaviruses. However, until the moment, there is not treatment or vaccine for these viral diseases, and a recent study demonstrated that these viruses are resistant to antiviral action of the ribavirin, a broad-spectrum antiviral drug (Livonesi et al, 2006).…”

The viral RNA capping machinery as a target for antiviral drugs

“…Ribavirin again is an effective inhibitor of Arenaviridae (Olschlager et al, 2011) and Bunyaviridae (Livonesi et al, 2006;Severson et al, 2003), but it has pleïotropic effects as discussed above and thus there is no direct evidence that the RNA cap snatching process is an actual target.…”

First report of antiviral activity of nordihydroguaiaretic acid against Fort Sherman-like virus (Orthobunyavirus)

“…The antiviral effect of NDGA and its derivatives has been reported in numerous studies, and the range of evaluated viruses is extensive (Gnabre et al, 1995;Huang et al, 2003;Hwu et al, 2008;Uchide et al, 2005;Park et al, 2003;Craigo et al, 2000;Konigheim et al, 2012). Some authors have associated the antiviral effect of NDGA with an inhibition of lipogenesis in some viruses, including arboviruses, which is necessary during viral replication.…”