I thought this was worthy of posting the a sub about ivermectin because ivermectin + doxycycline is emerging as a favored pairing in the fight against covid-19. We should learn a little about doxy.

This caught my attention:

[Doxy can] act as an ionophore help transport Zinc intracellularly, increasing cellular concentrations of Zinc to inhibit viral replication.

The HCQ crowd favor it in part because (I think) it is a zinc ionophore, which is "a substance which is able to transport particular ions across a lipid membrane in a cell.". HCQ helps zinc get into the cell, which is supposedly useful against covid-19.

It appears that doxy may have that same function.

Abstract:

This paper proposes both a rationale and potential study design for evaluation of low dose doxycycline (20mg BID) for the prevention of COVID-19 infection in exposed health care workers. [snip]

Doxycycline is a rational candidate drug to be evaluated for repurposing against SARS-CoV-2. Doxycycline is a generally safe tetracycline derivative that has been available for decades, most commonly dosed at 100mg BID to treat bacterial infections. However, in addition to its anti-microbial properties, doxycycline (and more generally tetracycline derivatives) may have a role as an effective anti-viral agent and as an anti-inflammatory drug. Early studies indicate potential efficacy of minocycline against respiratory syncytial virus (RSV) [12], and doxycycline against Dengue and Chikungunya infection[9, 10]. In addition, doxycycline is known or proposed to target several pathways that regulate viral replication. [13, 14, 15].

Doxycycline is a particularly attractive candidate as a COVID-19 prophylactic given it has been used in clinical practice for decades and maintains an excellent safety profile as demonstrated in multiple clinical studies. Any effective prophylaxis for COVID-19 should be able to demonstrate high efficacy at preventing infection and/or lowering severity of disease. Equally important, it should demonstrate this efficacy at dosing levels that are highly unlikely to precipitate any untoward severe side effects. Doxycycline has been selected based on its ability to:

1) inhibit metalloproteinases (MMPs), implicated in initial viral entry into the cell as well as in acute respiratory distress syndrome (ARDS) associated with severe COVID-19 infection [13, 16];

2) potential to inhibit Papain-like proteinase (PLpro) responsible for proteolytic cleavage of the replicase polyprotein to release non-structural proteins 1, 2 & 3 (Nsp1, Nsp2 and Nsp3) all essential for viral replication. [19];

3) potential to inhibit 3C-like main protease (3CLpro) or Nsp5 which is cleaved from the polyproteins causes further cleavage of Nsp4-16 and mediates maturation of Nsps which is essential in the virus lifecycle. [19];

4) act as an ionophore help transport Zinc intracellularly, increasing cellular concentrations of Zinc to inhibit viral replication. [6, 15];

5) inhibit Nf-kB which may lower inflammatory response to COVID-19 infection, and lower risk of viral entry due to decreasing DPP4 cell surface receptor. [20, 21];

6) inhibits (specifically low-dose doxycycline) expression of CD147/EMMPRIN that may be necessary for SARS-CoV-2 entry into T lymphocytes [22, 23].

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More doxy information from the 100 cases study covered here.

Doxycycline is an anti-inflammatory.

In vitro studies showed Doxycycline to exert anti inflammatory effects at low (20 - 40mg/day) and high (100 or 200mg/day) doses with inhibitory action on metalloproteases and modulating effects of pro inflammatory cytokines IL 6, IL 8 and tumor necrosis factor alpha. The anti inflammatory properties of Doxycycline and other components of tetracycline has been demonstrated for several inflammatory airway diseases, including, acute respiratory distress syndrome. Thereby, low Doxycycline doses have been shown to be more effective than high doses to prevent induction of pro inflammatory cytokines (such as IL 6) in inflammatory diseases13. Doxycycline is rapidly and almost completely absorbed after oral administration and has half life of 16-18 hours.

The turn from doxycycline to this confused me:

Based on the available evidence, we believe Tetracyclines may be effective agents in the treatment of Covid-19 due to their ability to chelate Zinc compounds on matrix metalloprotienases (MMP) on which coronaviruses rely heavily for survival, cell infiltration, cell to cell adhesion and replication, many of which has Zinc as part of their MMP complex.14

Until Google showed me that doxycycline is a kind of tetracycline, sort of:

Doxycycline is a synthetic (man-made) antibiotic derived from tetracycline.

Google further informs me that doxycycline can chelate zinc.

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There's a good comment about this on /r/covid19.

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