Montelukast is a dual-purpose inhibitor of SARS-CoV-2 infection and virus-induced IL-6 expression identified by structure-based drug repurposing

Luedemann, Max; Stadler, Daniela; Cheng, Cho-Chin; Protzer, Ulrike; Knolle, Percy; Donakonda, Sainitin

doi:10.1016/j.csbj.2022.01.024

Cited by 13 publications

(13 citation statements)

References 64 publications

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“…Молекулярно-динамическое моделирование показало, что монтелукаст будет нарушать структуру рецепторсвязывающего фрагмента S белка RBD SARS-CoV-2, соединяясь с областью, близкой к RBD (ARG-331, ASN-368, VAL-369, THR-404, SER-488) [33].…”

Section: противовирусные эффекты монтелукастаunclassified

“…Функциональная значимость монтелукаста против инфекции SARS-CoV-2 показана ингибированием инфекции in vitro. Монтелукаст предотвращал заражение SARS-CoV-2 (WT, бета-вариант, но не альфа-вариант) при высоких значениях IC50 выше 137,3 мкМ [33]. Поскольку монтелукаст действует как антагонист цистеиниллейкотриеновых рецепторов, предотвращая активацию клеток и выработку медиаторов воспаления, таких как IL-6, исследователи пришли к выводу о том, что монтелукаст может также снижать SARS-CoV-2-индуцированную экспрессию цитокинов иммунными клетками.…”

Section: противовирусные эффекты монтелукастаunclassified

“…Поскольку монтелукаст действует как антагонист цистеиниллейкотриеновых рецепторов, предотвращая активацию клеток и выработку медиаторов воспаления, таких как IL-6, исследователи пришли к выводу о том, что монтелукаст может также снижать SARS-CoV-2-индуцированную экспрессию цитокинов иммунными клетками. В эксперименте монтелукаст частично ингибировал выброс IL-6 и IL-8 лейкоцитами, индуцированный вирусом SARS-CoV-2 [33]. По мнению авторов эксперимента, монтелукаст контролирует высвобождение IL-6 непосредственно через блокирование лейкотриеновых рецепторов.…”

Section: противовирусные эффекты монтелукастаunclassified

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An Anti-Leukotriene Strategy to Reduce the Consequences of a Hyperinflammatory Response in COVID-19

Ищенко¹

2022

Рецепт

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В настоящее время пандемия COVID-19 стала серьезным вызовом для общественного здравоохранения. Сохраняются постоянные усилия по поиску терапевтических возможностей потенциальных методов лечения COVID-19. Однако, несмотря на все эти усилия, эффективной терапии до сих пор не существует, и это остается глобальной проблемой для научного сообщества. Важную роль в индукции и персистенции гипериммунного воспаления при COVID-19 играют лейкотриены. Антилейкотриеновая терапия является перспективным вариантом лечения COVID-19 и его последствий. Фаворитом здесь является блокатор лейкотриеновых рецепторов – монтелукаст. Имеющиеся на сегодняшний день результаты исследований обеспечивают четкое научное обоснование использования монтелукаста отдельно или в сочетании с противовирусной терапией при COVID-19. The COVID-19 pandemic has now become a major global public health disaster. There is persistence and ongoing efforts to find therapeutic options for potential treatments for COVID-19. However, despite all these efforts, there is still no effective therapy, and this remains a global problem for the scientific community. Leukotrienes play an important role in the induction and persistence of hyperimmune inflammation in COVID-19. Antileukotriene therapy is one of the attractive treatment options for COVID-19 and its consequences. The favorite here is the leukotriene receptor blocker – montelukast. The research results available to date provide a clear scientific rationale for the use of montelukast alone or in combination with antiviral therapy for COVID-19.

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Section: противовирусные эффекты монтелукастаunclassified

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An Anti-Leukotriene Strategy to Reduce the Consequences of a Hyperinflammatory Response in COVID-19

Ищенко¹

2022

Рецепт

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“…A computational simulation predicts that montelukast may bind S protein to disturb the RBD domain. 418 Montelukast sodium hydrate binds with the C-terminus domain of SARS-CoV-2 NSP1 protein to restore host protein synthesis, which is suppressed by NSP1. 419 , 420 …”

Section: Introductionmentioning

confidence: 99%

Metabolic alterations upon SARS-CoV-2 infection and potential therapeutic targets against coronavirus infection

Chen

et al. 2023

Sig Transduct Target Ther

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The coronavirus disease 2019 (COVID-19) caused by coronavirus SARS-CoV-2 infection has become a global pandemic due to the high viral transmissibility and pathogenesis, bringing enormous burden to our society. Most patients infected by SARS-CoV-2 are asymptomatic or have mild symptoms. Although only a small proportion of patients progressed to severe COVID-19 with symptoms including acute respiratory distress syndrome (ARDS), disseminated coagulopathy, and cardiovascular disorders, severe COVID-19 is accompanied by high mortality rates with near 7 million deaths. Nowadays, effective therapeutic patterns for severe COVID-19 are still lacking. It has been extensively reported that host metabolism plays essential roles in various physiological processes during virus infection. Many viruses manipulate host metabolism to avoid immunity, facilitate their own replication, or to initiate pathological response. Targeting the interaction between SARS-CoV-2 and host metabolism holds promise for developing therapeutic strategies. In this review, we summarize and discuss recent studies dedicated to uncovering the role of host metabolism during the life cycle of SARS-CoV-2 in aspects of entry, replication, assembly, and pathogenesis with an emphasis on glucose metabolism and lipid metabolism. Microbiota and long COVID-19 are also discussed. Ultimately, we recapitulate metabolism-modulating drugs repurposed for COVID-19 including statins, ASM inhibitors, NSAIDs, Montelukast, omega-3 fatty acids, 2-DG, and metformin.

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“…Montelukast, a leukotriene receptor antagonist safely used in asthma patients for many years, has the potential to inhibit SARS-CoV-2 and MERS-CoV infection [ 17 , 18 , 19 ] and has the ability to inhibit Zika virus infection by disrupting its integrity [ 20 ]. In this study, we found that montelukast could also effectively inhibit the infection of HCoV-OC43 by screening FDA-approved drugs.…”

Section: Introductionmentioning

confidence: 99%

Montelukast Inhibits HCoV-OC43 Infection as a Viral Inactivator

Chen

Wang

Shi

et al. 2022

Viruses

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Coronaviruses (CoVs) consist of a large group of RNA viruses causing various diseases in humans and in lots of animals. Human coronavirus (HCoV) OC43, the prototype of beta-coronavirus discovered in the 1960s, has been circulating in humans for long time, and infection with other emerging strains of beta-coronavirus (SARS-CoV, SARS-CoV-2, and MERS-CoV) can lead to severe illness and death. In this study, we found that montelukast, a leukotriene receptor antagonist, potently inhibited the infection of HCoV-OC43 in distinct cells in a dose- and time- dependent manner. Additionally, the results showed that montelukast induced release of HCoV-OC43 genomic RNA by disrupting the integrity of the viral lipid membrane, and irreversibly inhibited viral infection. Considering the similarity among HCoV-OC43, MERS-CoV, and SARS-CoV-2, it suggests that montelukast may be a potential candidate for the treatment of human beta-coronavirus infection.

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Montelukast is a dual-purpose inhibitor of SARS-CoV-2 infection and virus-induced IL-6 expression identified by structure-based drug repurposing

Abstract: Graphical abstract

Cited by 13 publications

References 64 publications

An Anti-Leukotriene Strategy to Reduce the Consequences of a Hyperinflammatory Response in COVID-19

An Anti-Leukotriene Strategy to Reduce the Consequences of a Hyperinflammatory Response in COVID-19

Metabolic alterations upon SARS-CoV-2 infection and potential therapeutic targets against coronavirus infection

Montelukast Inhibits HCoV-OC43 Infection as a Viral Inactivator

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