СОВРЕМЕННАЯ ЭТИОТРОПНАЯ ХИМИОТЕРАПИЯ ЦИТОМЕГАЛОВИРУСНОЙ ИНФЕКЦИИ ЧЕЛОВЕКА: КЛИНИЧЕСКАЯ ЭФФЕКТИВНОСТЬ, МОЛЕКУЛЯРНЫЙ МЕХАНИЗМ ДЕЙСТВИЯ, ЛЕКАРСТВЕННАЯ УСТОЙЧИВОСТЬ, НОВЫЕ ТЕНДЕНЦИИ И ПЕРСПЕКТИВЫ. ЧАСТЬ 2

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Вопросы вирусологии. 2018; 63: 250-260

СОВРЕМЕННАЯ ЭТИОТРОПНАЯ ХИМИОТЕРАПИЯ ЦИТОМЕГАЛОВИРУСНОЙ ИНФЕКЦИИ ЧЕЛОВЕКА: КЛИНИЧЕСКАЯ ЭФФЕКТИВНОСТЬ, МОЛЕКУЛЯРНЫЙ МЕХАНИЗМ ДЕЙСТВИЯ, ЛЕКАРСТВЕННАЯ УСТОЙЧИВОСТЬ, НОВЫЕ ТЕНДЕНЦИИ И ПЕРСПЕКТИВЫ. ЧАСТЬ 2

Андронова В. Л.

https://doi.org/10.18821/0507-4088-2018-63-6-250-260

Аннотация

Ряд синтетических соединений, таких как нуклеозидный аналог ганцикловир, его L-валиновый эфир (представляющий собой метаболический предшественник ганцикловира) и пирофосфатный аналог фоскарнет, разрешены ВОЗ для лечения заболеваний, вызываемых цитомегаловирусом (ЦМВ) человека, в европейском регионе. Биомишенью этих препаратов является вирусная ДНК-полимераза. Однако проведение стандартной анти-ЦМВ-терапии сопровождается тяжёлыми побочными эффектами, а также развитием у вируса лекарственной резистентности, главным образом в условиях иммунодефицита. В этом обзоре мы сконцентрировали внимание на вирусных протеинах, представляющих интерес в качестве новых потенциальных мишеней, и их ингибиторах, таких как ингибитор терминазы ЦМВ человека летермовир, показавший высокую активность в III фазе клинических испытаний, ингибиторы вирусной циклин-зависимой киназы (maribavir, cyclopropavir) и целый ряд соединений, проявляющих анти-ЦМВ-активность, проходящих доклинические испытания в эксперименте. Включение в стандартные профилактические и лечебные схемы новых анти-ЦМВ-агентов, активных против резистентных к ганцикловиру/фоскарнету штаммов ЦМВ, позволит значительно повысить эффективность терапии ЦМВ-инфекции, в том числе в случаях, когда стандартная терапия оказывается неэффективной. Области поиска: международные базы данных MEDLINE, PubMed, eLIBRARY.RU, ClinicalTrials.gov и другие с целью получения информации о соединениях, проявляющих селективное действие в отношении ЦМВ человека, наиболее перспективных для создания лекарственных препаратов.

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Problems of Virology. 2018; 63: 250-260

MODERN ETHIOTROPIC CHEMOTHERAPY OF HUMAN CYTOMEGALOVIRUS INFECTION: CLINICAL EFFECTIVENESS, MOLECULAR MECHANISM OF ACTION, DRUG RESISTANCE, NEW TRENDS AND PROSPECTS. PART 2

Andronova V. L.

https://doi.org/10.18821/0507-4088-2018-63-6-250-260

Abstract

A number of synthetic compounds, such as the nucleoside analog ganciclovir, its L-valine ester (a metabolic precursor of ganciclovir) and pyrophosphate analog foscarnet, are permitted for the treatment of HCMV-related diseases in the WHO European Region. The viral DNA- polymerase is used by all these drugs as a bio-target. However, the usage of standard anti-CMV therapy is accompanied by severe side effects, as well as the development of drug resistance in the virus, mainly in conditions of immunodeficiency. In this review, we focused on viral proteins of interest as new potential targets and their inhibitors, such as the inhibitor of human CMV terminology, lethermovir, which showed great activity in the third phase of clinical trials, inhibitors of viral cyclin-dependent kinase (maribavir, cyclopropavir ) and a number of compounds exhibiting anti-HCMV-activity, undergoing only preclinical trials in the experiment. Inclusion of new anti-CMV agents that are active against GСV/PFA/CDV-resistant strains of CMV into standard prophylactic and therapeutic regimens, will allow to increase the effectiveness of anti-CMV therapy, including in cases when standard therapy is ineffective. Areas covered: the international databases such as A MEDLINE, PubMed, eLIBRARY.RU, ClinicalTrials.gov., etc. with the purpose of obtaining information on compounds showing selective action against the human cytomegalovirus, the most promising for the development of drugs.

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