АНГИОТЕНЗИН-ПРЕВРАЩАЮЩИЙ ФЕРМЕНТ 2-ГО ТИПА, КАК МОЛЕКУЛЯРНЫЙ ПОСРЕДНИК ДЛЯ ИНФИЦИРОВАНИЯ КЛЕТКИ ВИРУСАМИ SARS-CoV И SARS-CoV-2
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Ключевые слова

ангиотензин-превращающий фермент 2-го типа
ренин-ангио- тензиновая система
протеаза TMPRSS2
SARS-CoV-2
SARS-CoV
протеаза ADAM17
ингибитор ангиотензин-превращающего фермента
блокатор ангиотензинового рецептора 1-го типа

Как цитировать

Шпаков, А. О. (2020). АНГИОТЕНЗИН-ПРЕВРАЩАЮЩИЙ ФЕРМЕНТ 2-ГО ТИПА, КАК МОЛЕКУЛЯРНЫЙ ПОСРЕДНИК ДЛЯ ИНФИЦИРОВАНИЯ КЛЕТКИ ВИРУСАМИ SARS-CoV И SARS-CoV-2. Российский физиологический журнал им. И. М. Сеченова, 106(7), 795–810. https://doi.org/10.31857/S0869813920060138

Аннотация

Для проникновения коронавируса SARS-CoV-2 (Severe Acute Respiratory Syndrome-CoronaVirus-2), возбудителя пандемии COVID-19, в клетку необходимо взаимодействие поверхностного шиповидного S-белка этого вируса с внеклеточным доменом мембранно-связанной формы ангиотензин-превращающего фермента 2-го типа (ACE2). Этот фермент, ключевое звено ренин-ангиотензиновой системы, отвечает за синтез ангиотензина-(1-7), наделенного вазодилаторными и противовоспалительными свойствами, из ангиотензина-II, мощного вазоконстриктора, синтез которого катализируется ангиотензин-превращающим ферментом (ACE), функциональным антагонистом ACE2. После сайт-специфичного гидролиза, осуществляемого локализованной в инфицируемой клетке трансмембранной сериновой протеазой TMPRSS2, вирусный S-белок специфично связывается с ACE2, что является триггером интернализации вируса в клетку путем эндоцитоза. Подавление этого процесса с помощью препаратов, ингибирующих протеазу TMPRSS2 и нарушающих взаимодействие S-белка с ACE2, позволяет предотвратить инфицирование и, тем самым, является перспективным подходом для лечения и профилактики COVID-19. Сходный механизм проникновения в клетку использует и вирус SARS-CoV, возбудитель атипичной пневмонии, родственный SARS-CoV-2. При лечении пациентов с артериальной гипертензией и сахарным диабетом с помощью ACE-ингибиторов, блокаторов ангиотензиновых рецепторов, статинов и некоторых антидиабетических препаратов экспрессия и активность ACE2, как правило, повышаются, что увеличивает риск заражения SARS-CoV-2 и ухудшает исход заболевания. В процессе инфицирования вирус, образуя комплекс с ACE2, снижает количество ACE2 на поверхности клеток, нарушает зависимые от ACE2 физиологические процессы, и это является одной из причин острого респираторного дистресс-синдрома и сердечной недостаточности у больных COVID-19. В настоящем обзоре анализируется функциональная роль ACE2 в инфицировании клеток вирусами SARS-CoV-2 и SARS-CoV, а также обсуждаются молекулярные механизмы этого процесса и его патофизиологические последствия.

https://doi.org/10.31857/S0869813920060138
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