Tetrasykliinin mahdollinen hyöty COVID-19 taudissa

• Covid-19 taudin kulussa aktivoituu myös   matrixmetalloproteaaseja (MMP) , jotka kelaavat sinkkiä  kehoproteiineista.

 

• Lähde: Bansode et Losso: In vitro inhibition of angiogenesis by phytic acid: Interaction with gelatinase A , MMP-2.

 Esimerkiksi MMP-2 on gelatinaasiA  ja  hajoittaatyypin IV kollageenia .Jos pystytään  estämään että pro-MMP2 ei pääse aktivoitumaan  voidaan viivästyttää solukalvon  hajoamista,  esim angiogeneesissä  ja tuumoriprogressiossa ja metastaaseissa.  Pro-MMP  erittyy inaktiivina zymogeenina, jonka aktivoi  kymaasi.    Ravintoaineissa on löydetty  tekijää, joka on MMP2 -gelatinaasin luonnolinen estäjä ja pystyy estämään aktivoituneen pro-MMP-2:n  hajoittavan vaikutuksen.  Tämä  estävä ravintoaine on fytiini (phytic acid)  eli  inositolihexafosfaatti.   Se on tunnettu sikäli antinutrienttina, että se  pystyi estämään  gelatinolyyttistä  aktivoitunutta  matrixmetalloproteaasia MMP-2:ta   

• MMP-1 estäjä.   https://pubmed.ncbi.nlm.nih.gov/15269538/?from_term=Bansode+R+R.%2C+Losso+J.N.+&from_pos=7

• The Bowman‐Birk inhibitor. Trypsin‐ and chymotrypsin‐inhibitor from soybean YEHUDITH BIRK  Y BirkThe significance of BBI as a prototype of a family of inhibitors present in all legume seeds is discussed. DOI: 10.1111/j.1399-3011.1985.tb02155.x 

 

• The Biochemical and Functional Food Properties of the Bowman-Birk InhibitorJack N Losso  ¹  DOI: 10.1080/10408390601177589

 Abstract

The Bowman-Birk inhibitor (BBI) is a small water-soluble protein present in soybean and almost all monocotyledonous and dicotyledonous seeds. The molecular size of BBI ranges from 1,513 Da to about 20,000 Da. BBI is to seeds what alpha(1)-antitrypsin is to humans. Soy-based food products rich in BBI include soybean grits, soymilk, oilcake, soybean isolate, and soybean protein concentrate. BBI is stable within the pH range encountered in most foods, can withstand boiling water temperature for 10 min, resistant to the pH range and proteolytic enzymes of the gastrointestinal tract, bioavailable, and not allergenic. BBI reduces the proteolytic activities of trypsin, chymotrypsin, elastase, cathepsin G, and chymase, serine protease-dependent matrix metalloproteinases, urokinase protein activator, mitogen activated protein kinase, and PI3 kinase, and upregulates connexin 43 (Cx43) expression. Several studies have demonstrated the efficacy of BBI against tumor cells in vitro, animal models, and human phase IIa clinical trials. FDA considers BBI as a drug. In 1999, FDA allowed a health claim on food labels stating that a daily diet containing 25 grams of soy protein, also low in saturated fat and cholesterol, may reduce the risk of heart disease [corrected] This review highlights the biochemical and functional food properties of the Bowman-Birk inhibitor.

• Myös tetrasykliini  suojaa matrixmetalloproteinaasien  hajoittavalta vaikutukselta kudoksia.

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

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.