ABSTRACT
The study of antigen-antibody interaction on the model of Epstein-Barr virus (EBV) and second type adenovirus (Ad2) based on the surface plasmon resonance (SPR) was carried out. Kinetic and concentration dependences between virus antigens and specific antisera to them at different pH were determined. Experimental samples of biosensors for the detection by SPR method of virus (EBV and Ad2) antigens using monospecific antibodies, immobilized on the surface of gold, and also for detection of specific antibodies in the blood sera of patients with EBV or adenovirus infection were elaborated
Subject(s)
Adenoviruses, Human/immunology , Antibodies, Viral/immunology , Antigen-Antibody Complex/analysis , Antigens, Viral/immunology , Biosensing Techniques/methods , Herpesvirus 4, Human/immunology , Adenoviruses, Human/isolation & purification , Antigen-Antibody Complex/immunology , Cell Line, Tumor , Herpesvirus 4, Human/isolation & purification , Humans , Immunoenzyme Techniques , Microscopy, Electron , Sensitivity and Specificity , Spectrophotometry , Surface Plasmon ResonanceABSTRACT
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.
Subject(s)
Adenoviridae Infections/drug therapy , Antiviral Agents/therapeutic use , Azacitidine/analogs & derivatives , Adenoviridae Infections/pathology , Adenoviruses, Human/drug effects , Animals , Animals, Newborn , Azacitidine/pharmacology , Azacitidine/therapeutic use , Cricetinae , Disease Models, Animal , Mesocricetus , Spleen/drug effects , Spleen/pathologyABSTRACT
The search for the inhibitors of adenoviruses has been performed among the substances of new class NCM (nitrogen containing macroheterocycles) and their analogues that have high potential of pharmacological properties. We have found a number of NCM and their derivatives that inhibit the reproduction of adenoviruses to various degrees. For the prediction of NCM structure with antiadenoviral activity we have performed the computer modeling using QSAR approach on the basis of simplex representation of molecular structure (SiRMS).
