1. Сибирский государственный медицинский университет, Томск, Россия 2. Сибирский государственный медицинский университет, Томск, Россия; Научно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр, Томск, Россия
Пандемия коронавирусной инфекции дала стимул появлению многочисленных публикаций, посвящённых α1-протеиназному ингибитору (α1-ПИ, α1-антитрипсин), особенно когда было выявлено, что высокая смертность населения некоторых регионов соответствует географической локализации дефицитных аллелей α1-ПИ. По аналогии с данными прошлого столетия, когда была доказана первопричина генетического дефицита α1-антитрипсина, приводящая к активации эластазы при эмфиземе лёгких, можно предположить, что гиперактивация протеолиза при COVID-19 связана с нарушением функционирования α1-ПИ. Цель настоящего обзора заключается в систематизации научных данных о роли α1-ПИ как диагностического маркера и/или средства таргетной терапии в условиях гиперактивации протеолиза при инфицировании SARS-CoV-2 и определении ключевых направлений трансляционных исследований ингибиторов протеиназ. В работе дана характеристика протеиназозависимых стадий вирусной инфекции: рецепция и проникновение вируса внутрь клетки, дисбаланс ангиотензин-рениновой, кининовой, свертывающей и фибринолитической протеолитических систем плазмы крови. Рассмотрена роль ангиотензинпревращающего фермента 2 (ACE2), мембрано-связанной сериновой протеазы (TMPRSS), металлопротеазы ADAM17, фурина, катепсинов, трипсино- и эластазоподобных сериновых протеиназ в регуляции тропности вируса, активации протеолитических каскадов плазмы крови, развитии осложнений коронавирусной инфекции. Проведён анализ данных по участию α1-ПИ в патогенезе коронавирусной инфекции, взаимосвязи со степенью тяжести COVID-19 и коморбидными заболеваниями. Особое внимание уделено роли приобретённого дефицита α1-ПИ при оценке состояния больных в условиях гиперактивации протеолиза на фоне хронических заболеваний, формирования факторов риска прогрессирования сопутствующей патологии и развития отдалённых последствий COVID-19. Пронализированы данные по поиску и применению лекарственных средств, обладающих ингибиторной активностью при терапии заболеваний бронхолёгочной, сердечно-сосудистой систем. Представлены доказательства наличия противовирусного, противовоспалительного, антикоагулянтного, антиапоптотического эффекта α1-ПИ и перспектив использования его в качестве таргетного препарата при лечении коронавирусной инфекции.
Акбашева О.Е. и др. Протеолиз и дефицит α1-протеиназного ингибитора при инфекции SARS-CoV-2 // Биомедицинская химия. - 2022. - Т. 68. -N 3. - С. 157-176.
Акбашева О.Е. и др., "Протеолиз и дефицит α1-протеиназного ингибитора при инфекции SARS-CoV-2." Биомедицинская химия 68.3 (2022): 157-176.
Акбашева, О. Е., Спирина, Л. В., Дьяков, Д. А., Масунова, Н. В. (2022). Протеолиз и дефицит α1-протеиназного ингибитора при инфекции SARS-CoV-2. Биомедицинская химия, 68(3), 157-176.
Переводная версия в журнале «Biomedical Chemistry (Moscow) Supplement Series B»:10.1134/S1990750822040035
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