Effects of 2-Deoxy- d -Glucose and 3-Deazauridine Individually and in Combination on the Replication of Japanese B Encephalitis Virus

Abstract

We have tested the potencies of the competitors of glucose, 2-deoxy-i>.glucose, and of uridine, 3-deazauridine, on the inhibition of Japanese B encephalitis virus multiplication in BHK-21 cell cultures. The relative effectiveness of the viral inhibitors were evaluated individually and in combination in relation to cytotoxicity as a measure of the selectivity of inhibition. When the drugs were administered individually, the antiviral activity was masked by the cytotoxic effect on the host. By combining the two drugs, it was possible to inhibit Japanese encephalitis virus production at noncytotoxic concentrations. The effects of 2-deoxy-D-glucose and 3-deazauridine on the growth inhibition of BHK-21 cells in cultures were only additive, while they were clearly synergistic on the inhibition of Japanese encephalitis virus production. Thus, it was possible 'to achieve an increased antiviral effect without a significant increase in cytotoxicity. Although the precise biochemical mechanism of the antiviral activity of these antimetabolites in combination is not known, our results indicate the potential value of this approach in viral chemotherapy.

Beta Interferon Regulation of Glucose Metabolism Is PI3K/Akt Dependent and Important for Antiviral Activity against Coxsackievirus B3

“…Previous publications have identified that treatment of cells with 2-DG reduces the replication of a variety of viruses, including CVB3 (77)(78)(79)(80)(81)(82)(83). Limiting the energy supplies in an infected cell would affect protein synthesis and the assembly of viral progeny.…”

Discovery of Novel Ribonucleoside Analogs with Activity against Human Immunodeficiency Virus Type 1

“…Our study, to the best of our knowledge, is the first to demonstrate the antiretroviral activity of formycin A. Many previous studies identified the activity of 3-deazauridine against riboviruses (20)(21)(22)(23)(24)(25)(26) and retroviruses (23,27). Interestingly, 3-deazauridine was previously observed to potentiate the anti-HIV-1 activity of 3TC and dideoxycytosine (28).…”

Use of 2-deoxy-D-glucose in virology research: A mini review

“…This study reported that 2-DG intervenes in the synthesis and elongation of oligosaccharides in the viral envelope glycoproteins. Based on this pioneering study, many experimental studies pertaining to inhibition of viral infection by 2-DG was explored subsequently, which included viruses belonging to the family of Paramyxoviridae, Rhabdoviridae, Togaviridae (Kaluza et al, 1972) [10] , Herepesviridae (Courtney et al, 1973) [4] , Flaviviridae (Woodman et al, 1977) [23] , Adenoviridae (Xi et al 2014) [26] and Retroviridae (Blough et al, 1986) [2] .…”

“…Experimentation of 2-DG in viral replication has been reported since the late 1950s, with the first report on the significant reduction of influenza virus concentration in the chorio-allantoic membrane of embryonated chicken egg (Kilbourne, 1959) [12] . Ever since then, 2-DG has been explored as an anti-viral agent in Herpesviridae (Courtney et al, 1973;Radsak et al, 1981) [4,17] , Flaviviridae (Woodman et al, 1977) [23] , Orthomyxoviridae (Kaluza et al, 1972;Kilbourne, 1959) [10,12] , Rhabdoviridae (Kaluza et al, 1972) [10] , Retroviridae, Paramyxoviridae (Tripathy and Mohanty, 1979) [21] , Togaviridae (Kaluza et al, 1972) [10] and Picornaviridae. The details of previous studies detailing the effect of 2-DG on various viruses have been tabulated (Table 1).…”