Would Repurposing Minocycline Alleviate Neurologic Manifestations of COVID-19?

Oliveira, Aline Cristina; Richards, Elaine M.; Karas, Marianthi M.; Pepine, Carl J.; Raizada, Mohan K.

doi:10.3389/fnins.2020.577780

Cited by 9 publications

(7 citation statements)

References 46 publications

(66 reference statements)

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“…Among the most interesting results, we identified minocycline, an antibiotic, and anti‐inflammatory drug targeting CASP3 and TNF . Minocycline has been very recently proposed to alleviate the effects of SARS‐CoV‐2 severe infection in the central nervous system (Oliveira et al, 2020) (see extended results in Appendix 2).…”

Section: Resultsmentioning

confidence: 99%

Integrated intra‐ and intercellular signaling knowledge for multicellular omics analysis

Türei

Valdeolivas

Gul

et al. 2021

Molecular Systems Biology

198

169

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Molecular knowledge of biological processes is a cornerstone in omics data analysis. Applied to single-cell data, such analyses provide mechanistic insights into individual cells and their interactions. However, knowledge of intercellular communication is scarce, scattered across resources, and not linked to intracellular processes. To address this gap, we combined over 100 resources covering interactions and roles of proteins in inter-and intracellular signaling, as well as transcriptional and post-transcriptional regulation. We added protein complex information and annotations on function, localization, and role in diseases for each protein. The resource is available for human, and via homology translation for mouse and rat. The data are accessible via OmniPath's web service (https://omnipathdb.org/), a Cytoscape plug-in, and packages in R/Bioconductor and Python, providing access options for computational and experimental scientists. We created workflows with tutorials to facilitate the analysis of cell-cell interactions and affected downstream intracellular signaling processes. OmniPath provides a single access point to knowledge spanning intraand intercellular processes for data analysis, as we demonstrate in applications studying SARS-CoV-2 infection and ulcerative colitis.

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Section: Resultsmentioning

confidence: 99%

Integrated intra‐ and intercellular signaling knowledge for multicellular omics analysis

Türei

Valdeolivas

Gul

et al. 2021

Molecular Systems Biology

198

169

View full text Add to dashboard Cite

show abstract

“…This knowledge would be valuable to mitigate harmful CNS outcomes of COVID-19 pandemic, and possibly its long-term consequences on neurodevelopmental, psychiatric, and neurodegenerative conditions. Alternatively, although this awaits further research, in critical groups, for instance, aged individuals or cohorts with pre-existing conditions, modulating the pro-inflammatory activity of microglia upon SARS-CoV-2 detection, via minocycline ( Oliveira et al, 2020 ), for example, may help avoid unwanted neurological outcomes. The same holds for individuals with a history of mental health disorders, for which the reduction of dysfunctional microglial synaptic remodeling may prevent the worsening of mental distress associated with the pandemic.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, similar to what was previously discussed in section “Putative Responses of Microglia to SARS-CoV-2 CNS Infection” (regarding depleting microglia during CNS viral infection), while completely disrupting microglial function can worsen injury recovery, down-regulating their inflammatory response can be protective. Of note, minocycline treatment has been proposed for COVID-19 ( Oliveira et al, 2020 ).…”

Section: Microglia Could Determine How the Cns Is Affected By Covid-1mentioning

confidence: 99%

Microglia Fighting for Neurological and Mental Health: On the Central Nervous System Frontline of COVID-19 Pandemic

Andrade

Šimončičová

Carrier

et al. 2021

Front. Cell. Neurosci.

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Coronavirus disease 2019 (COVID-19) is marked by cardio-respiratory alterations, with increasing reports also indicating neurological and psychiatric symptoms in infected individuals. During COVID-19 pathology, the central nervous system (CNS) is possibly affected by direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invasion, exaggerated systemic inflammatory responses, or hypoxia. Psychosocial stress imposed by the pandemic further affects the CNS of COVID-19 patients, but also the non-infected population, potentially contributing to the emergence or exacerbation of various neurological or mental health disorders. Microglia are central players of the CNS homeostasis maintenance and inflammatory response that exert their crucial functions in coordination with other CNS cells. During homeostatic challenges to the brain parenchyma, microglia modify their density, morphology, and molecular signature, resulting in the adjustment of their functions. In this review, we discuss how microglia may be involved in the neuroprotective and neurotoxic responses against CNS insults deriving from COVID-19. We examine how these responses may explain, at least partially, the neurological and psychiatric manifestations reported in COVID-19 patients and the general population. Furthermore, we consider how microglia might contribute to increased CNS vulnerability in certain groups, such as aged individuals and people with pre-existing conditions.

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“…Therefore, early treatment with TCs, mainly doxycycline or minocycline, for high-risk COVID-19 patients seems linked to an early recovery, reduced hospitalization, and decreased mortality rate. Oliveira et al (2020), in a clinical trial study, demonstrated that lopinavir plus doxycycline is more effective in the management of COVID-19 patients due to a synergistic inhibition of SARS-CoV-2 protease. Nevertheless, Cag et al (2020) showed that combination of minocycline and chloroquine offers many benefits in the management of moderate-to-severe COVID-19 patients, since both drugs are widely available and cheap, and their contraindications are well-known and recognized.…”

Section: Anti-inflammatory Effects Of Tetracyclines In Covid-19mentioning

confidence: 99%

Pleiotropic Effects of Tetracyclines in the Management of COVID-19: Emerging Perspectives

et al. 2021

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Coronavirus disease 2019 (COVID-19) is a global infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 15% of severe cases require an intensive care unit (ICU) admission and mechanical ventilation due to development of acute respiratory distress syndrome (ARDS). Tetracyclines (TCs) are a group of bacteriostatic antibiotics, like tetracycline, minocycline, and doxycycline, effective against aerobic and anaerobic bacteria as well as Gram-positive and Gram-negative bacteria. Based on available evidences, TCs may be effective against coronaviruses and thus useful to treat COVID-19. Thus, this review aims to provide a brief overview on the uses of TCs for COVID-19 management. SARS-CoV-2 and other coronaviruses depend mainly on the matrix metalloproteinases (MMPs) for their proliferation, cell adhesion, and infiltration. The anti-inflammatory mechanisms of TCs are linked to different pathways. Briefly, TCs inhibit mitochondrial cytochrome c and caspase pathway with improvement of lymphopenia in early COVID-19. Specifically, minocycline is effective in reducing COVID-19–related complications, through attenuation of cytokine storm as apparent by reduction of interleukin (IL)-6, IL-1, and tumor necrosis factor (TNF)-α. Different clinical trials recommend the replacement of azithromycin by minocycline in the management of COVID-19 patients at high risk due to two main reasons: 1) minocycline does not prolong the QT interval and even inhibits ischemia-induced arrhythmia; 2) minocycline displays synergistic effect with chloroquine against SARS-CoV-2. Taken together, the data presented here show that TCs, mainly doxycycline or minocycline, may be potential partners in COVID-19 management, derived pneumonia, and related complications, such as acute lung injury (ALI) and ARDS.

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Would Repurposing Minocycline Alleviate Neurologic Manifestations of COVID-19?

Cited by 9 publications

References 46 publications

Integrated intra‐ and intercellular signaling knowledge for multicellular omics analysis

Integrated intra‐ and intercellular signaling knowledge for multicellular omics analysis

Microglia Fighting for Neurological and Mental Health: On the Central Nervous System Frontline of COVID-19 Pandemic

Pleiotropic Effects of Tetracyclines in the Management of COVID-19: Emerging Perspectives

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