COVID-19 ja MMPs : Olisiko tetrasykliineistä stabiloijaa?

https://www.eurotimes.org/tetracyclines-proposed-as-treatment-for-covid-19/

Abstract

Currently there is a race against time to identify prophylactic and therapeutic treatments against COVID‐19. Until these treatments are developed, tested and mass produced, it might be prudent to look into existing therapies that could be effective against this virus. Based on the available evidence we believe that tetracyclines may be effective agents in the treatment of COVID‐19. Tetracyclines (e.g. tetracycline, doxycycline, and minocycline) are highly lipophilic antibiotics that are known to chelate zinc compounds on matrix metalloproteinases (MMPs)¹. Coronaviruses are also known to heavily rely on host MMPs for survival, cell infiltration, cell to cell adhesion, and replication, many of which have zinc as part of their MMP complex^2,3. It is possible that the zinc chelating properties of tetracyclines may also aid in inhibiting COVID‐19 infection in humans limiting their ability to replicate within the host.

   Tetracyclines proposed as treatment for COVID-19
    In a letter to the editor of Pharmacotherapy , Mohit Sodhi, MSc, and Mahyar Etminan, PharmD, from the Department of  Ophthalmology and Visual Sciences at the University of British Columbia,
 Vancouver, Canada outline evidence supporting the therapeutic potential  of tetracyclines as a treatment for patients with COVID-19. The letter  was published online on April 8, 2020.

https://accpjournals.onlinelibrary.wiley.com/doi/abs/10.1002/phar.2395
The rationale for using tetracyclines considers the lipophilic nature of the tetrayclines along with their ability to inhibit matrix  metalloproteinases (MMPs), anti-inflammatory properties and possible
antiviral activity. Furthermore, the authors cite the relative safety of  tetracyclines compared with other agents that are being considered to treat COVID-19, including antimalarial and antiretroviral drugs.
Describing the tetracyclines as a potential treatment for COVID-19  “that is hiding in plain sight”, Sodhi and Etminan urge researchers to  consider investigating the efficacy of this available therapy.
Reviewing the activity of tetracyclines, the authors explain that  they chelate zinc compounds on MMPs. Because coronaviruses depend on those enzymes for survival, cell infiltration, cell-to-cell adhesion,  and replication, Sodhi and Etminan postulated that tetracyclines might
inhibit viral replication within the host.
As further support for the antiviral activity of tetracyclines, they cited reports indicating that tetracyclines might have activity for  inhibiting RNA replication on positive-sense single stranded RNA, like SARS-CoV-2, the COVID-19 viral pathogen. The evidence includes findings
from one in vitro study showing that doxycycline inhibited dengue virus serine protease, viral replication and viral entry into cultured cells and another showing a 70% decrease in retroviral load when a murine retrovirus producing cell line was incubated with
doxycycline.
Anti-inflammatory activity of tetracyclines is well-recognised and  includes the ability to downregulate expression of several inflammatory cytokines that have been shown to be significantly elevated in lung  tissue exposed to the coronavirus causing the infection known as SARS.
In addition, chemically modified tetracyclines have been shown to induce apoptosis of mast cells that release a host of pro-inflammatory mediators. The effect on mast cells may be particularly relevant for treating COVID-19 considering evidence that mast cell proliferation
within respiratory submucosa is induced by coronaviruses.
The lipophilic nature of tetracyclines favors their distribution into lung tissue and is also significant because SARS-CoV-2 has a lipophilic  outer shell. Suggesting that tetracyclines might be useful treatment  for pulmonary complications of COVID-19, the authors cite a preclinical
study in which a chemically-modified tetracycline prevented sepsis induced by acute respiratory distress syndrome.<
   
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national recommendations and guidelines. Please send all your items to
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Tetracyclines proposed as treatment for COVID-19

In a letter to the editor of Pharmacotherapy , Mohit Sodhi, MSc, and Mahyar Etminan, PharmD, from the Department of Ophthalmology and Visual Sciences at the University of British Columbia, Vancouver, Canada outline evidence supporting the therapeutic potential of tetracyclines as a treatment for patients with COVID-19. The letter was published online on April 8, 2020.
https://accpjournals.onlinelibrary.wiley.com/doi/abs/10.1002/phar.2395
The rationale for using tetracyclines considers the lipophilic nature of the tetrayclines along with their ability to inhibit matrix metalloproteinases (MMPs), anti-inflammatory properties and possible antiviral activity. Furthermore, the authors cite the relative safety of tetracyclines compared with other agents that are being considered to treat COVID-19, including antimalarial and antiretroviral drugs.
Describing the tetracyclines as a potential treatment for COVID-19 “that is hiding in plain sight”, Sodhi and Etminan urge researchers to consider investigating the efficacy of this available therapy.
Reviewing the activity of tetracyclines, the authors explain that they chelate zinc compounds on MMPs. Because coronaviruses depend on those enzymes for survival, cell infiltration, cell-to-cell adhesion, and replication, Sodhi and Etminan postulated that tetracyclines might inhibit viral replication within the host.
As further support for the antiviral activity of tetracyclines, they cited reports indicating that tetracyclines might have activity for inhibiting RNA replication on positive-sense single stranded RNA, like SARS-CoV-2, the COVID-19 viral pathogen. The evidence includes findings from one in vitro study showing that doxycycline inhibited dengue virus serine protease, viral replication and viral entry into cultured cells and another showing a 70% decrease in retroviral load when a murine retrovirus producing cell line was incubated with doxycycline.
Anti-inflammatory activity of tetracyclines is well-recognised and includes the ability to downregulate expression of several inflammatory cytokines that have been shown to be significantly elevated in lung tissue exposed to the coronavirus causing the infection known as SARS. In addition, chemically modified tetracyclines have been shown to induce apoptosis of mast cells that release a host of pro-inflammatory mediators. The effect on mast cells may be particularly relevant for treating COVID-19 considering evidence that mast cell proliferation within respiratory submucosa is induced by coronaviruses.
The lipophilic nature of tetracyclines favors their distribution into lung tissue and is also significant because SARS-CoV-2 has a lipophilic outer shell. Suggesting that tetracyclines might be useful treatment for pulmonary complications of COVID-19, the authors cite a preclinical study in which a chemically-modified tetracycline prevented sepsis induced by acute respiratory distress syndrome.

We want to hear from you with stories, suggestions or ideas, national recommendations and guidelines. Please send all your items to COVID19@escrs.org or use wetransfer.com for larger files