Effect of 6-Azacytidine on the Course of Experimental Adenoviral Infection in Newborn Syrian Hamsters

Abstract

Adenoviral infection is a serious human pathology leading to respiratory, gastrointestinal and ocular disorders and epidemic outbreaks, especially in children's groups. Here we present the results from an investigation of anti- adenoviral effect of 6-azacytidine (6-AC) both in vitro and in vivo. The selectivity index of 6-AC for adenovirus type 5 in HEp-2 cells was 374, the 50% effective concentration was 0.5 mg/ml. For in vivo investigations we developed a model of disseminated adenoviral infection in newborn Syrian hamsters. The infectious virus was recovered from the liver, kidney, lungs and heart. Application of 6-AC led to a reduced period of the virus presence (7 days in the liver and 4 days in the kidney and heart) and lowered virus titers on day 3 post-inoculation (p.i.) (liver - 2.7 and 4.1, heart - 0 and 3.2, kidney - 0 and 2.4 log(10 )CPD(50)/mg tissue weight, in the presence and absence of 6-AC, respectively). Application of 6-AC to newborn Syrian hamsters led to partial destruction of their splenocytes. The results obtained suggest that 6-AC or 6-ACbased drugs with lower toxicity or applied topically may be suitable for therapy and prevention of adenoviral infection in humans.

Hexadecyloxypropyl-cidofovir, CMX001, prevents adenovirus-induced mortality in a permissive, immunosuppressed animal model

“…Several animal models have been proposed that are to some extent permissive for human Ad replication, including cotton rats (30,31), pigs (32), dogs (33), and Syrian hamsters (34)(35)(36). However, these studies did not address replication of Ad under conditions of immunosuppression, as is observed in transplant patients.…”

Adsorption of Cytosine and AZA Derivatives of Cytidine on Au Single Crystal Surfaces

“…All three carbon atoms in this molecule are bonded to one, two or three electronegative partners, and so have high binding energies. In 6-azacytidine, the peak A at about 288.3 eV corresponds to the same peak in 6-azacytosine, assigned to the urea carbon C (2) , and with C (4) and C (5) at 0.5 and 1.9 eV lower binding energy respectively. 6-azacytidine contains 8 carbon atoms in total, and these mainly contribute to the strongest peak C. The overall agreement between theory and experiment is satisfactory.…”

“…The shifts of the other two core levels, C (4) and C (6) , are attributed to indirect effects of hydrogen bonding and chemical interaction with the surface. The N 1s and C 1s spectra of vacuum deposited cytosine are very similar for Au(111) and (110), although the O 1s spectrum shows a significant difference in energy between the two surfaces.…”

“…In its isomer 5-azacytidine (5-azaC) the C (5) -H group is exchanged with the N (5) atom in the pyrimidine ring. Both 6-azaC and 5-azaC nucleosides have a wide spectrum of biological properties that result in pharmacological activity, primarily antitumor and antiviral effects [1][2][3][4][5][6][7] . There have been extensive experimental [8][9][10][11][12][13][14][15][16][17] and theoretical [18][19][20] studies of biomolecules on gold and other Group 11 metal surfaces, to a large extent focused on amino acids, nucleobases, and their polymers -oligonucleotides, peptides, proteins, etc.…”

Synthesis and Comparative Study of Anti-Adenoviral Activity of 6-Azacytidine and Its Analogues

“…[6,7] More recent research on antiviral properties of 6-azaСyd has demonstrated its high activity relative to human AdV in vitro and in vivo systems. [8][9][10][11][12][13] In cell cultures, the anti-adenoviral effect of 6-azaСyd was expressed by inhibiting the formation of virus-specific intranuclear DNA-containing inclusion bodies, the synthesis of viral proteins and infectious virus. [12,14] The application of 6-azaСyd on a model of disseminated AdV infection in newborn Syrian hamsters led to significant decrease of virus titer and shortening of the time of virus clearance in organs.…”