The Virus Mutants Resistant to Chemotherapeutics—A Main Problem in the Treatment of Viral Infections

Abstract

ABSTRACTThe discovery and development of effective antiviral chemoterapeutics is of major importance for the successful treatment of viral infections. However, in many cases, their utility is limited by the emergence of resistant mutants. The knowledge of the mechanisms of drug resistance is of principle importance for the control of this phenomenon. Here are reviewed the resistance characteristics in all group of antivirals versus HIV, herpes simplex virus, influenza virus and enteroviruses. The failure of aciclovir therapy against herpes simplex virus infections is found to be a result of emergence of thymidine kinase negative viral mutants and mutants in the gene coding DNA polymerase. Drug resistance was registered in the anti-HIV chemotherapeutic agents, as well. With regard to this the successful therapeutic approach of the “triple cocktail therapy” (nucleoside inhibitor/nonnucleoside inhibitor/protease inhibitor) has been introduced. Influenza virus mutants resistant to the two groups of registered anti-flu chemoterapeutics (amantane derivates, binding viral M2 protein, and virus neuraminidase inhibitors) have been observed. Resistant mutants have been also registered to mopyridone, influenza virus A and B replication inhibitor, binding M1 protein. The lack of clinically effective antivirals versus enterovirus infections could be explained with the existence of virus progeny consisting of numerous mutants with various point mutations, the so called pseudospecies.This phenomenon is illustrated with experimental data obtained in the Institute of Microbiology BAS on the model of Coxsackievirus B1 infection in newborn mice.