Estrogen antagonists may be a viable treatment for Ebola

[nograde]

... and it's not exactly a secret. From http://en.m.wikipedia.org/wiki/Ebola_virus_disease:

The Estrogen receptor drugs used to treat infertility and breast cancer (clomiphene and toremifene) inhibit the progress of Ebola virus in infected mice.Ninety percent of the mice treated with clomiphene and fifty percent of those treated with toremifene survived the tests.[...] Given their oral availability and history of human use, these drugs would be candidates for treating Ebola virus infection in remote geographical locations, either on their own or together with other antiviral drugs.

 

[Such_Saturation]

Reminds me of that study with thyroxine and herpes [Effects of hypo- and hyperthyroid states on herpes simplex virus infectivity in the rat.]

Actually, <<A 2014 study found that Amiodarone, an ion channel blocker used in the treatment of heart arrhythmias, blocks the entry of ebola virus into cells in vitro.>>

<<Amiodarone chemically resembles thyroxine (thyroid hormone), and its binding to the nuclear thyroid receptor might contribute to some of its pharmacologic and toxic actions>>

 

[LucyL]

... and it's not exactly a secret. From http://en.m.wikipedia.org/wiki/Ebola_virus_disease:

The Estrogen receptor drugs used to treat infertility and breast cancer (clomiphene and toremifene) inhibit the progress of Ebola virus in infected mice.Ninety percent of the mice treated with clomiphene and fifty percent of those treated with toremifene survived the tests.[...] Given their oral availability and history of human use, these drugs would be candidates for treating Ebola virus infection in remote geographical locations, either on their own or together with other antiviral drugs.

Nitric oxide could be one of the linking pieces.

Ray Peat wrote in Estrogen and Osteoporosis

Estrogen increases production of nitric oxide systemically, and nitric oxide can stimulate TNF formation.

and in private correspondence, as I noted here he wrote

Ebola infection seems to involve a lack of interferon, and the amount of nitric oxide in the blood increases in proportion to the intensity of the symptoms. Reductive stress/inflammation that activates interleukin-1 and arachidonic acid metabolites can inhibit interferon, and at the same time increase the production of nitric oxide. Resistance would be improved by oxidative and antiinflammatory things.

Is there anything bad estrogen isn't involved in?

 

[Suikerbuik]

How do you define estrogen antagonists?

From the actual study:

Therefore, we performed an in vitro screen of Food and Drug Administration (FDA)– and ex–US-approved drugs and selected molecular probes to identify drugs with antiviral activity against the type species Zaire ebolavirus (EBOV). From this screen, we identified a set of selective estrogen receptor modulators (SERMs), including clomiphene and toremifene, which act as potent inhibitors of EBOV infection

Together, these data suggest that clomiphene and toremifene are acting through a pathway independent of the classical estrogen signaling pathway.

So if estrogen antagonists are defined as drugs opposing the estrogen receptor and if these drugs do not affect cellular estrogen levels. Then I am not so sure if this has much relevance. The study that finds these drugs to be helpful, also says that these drugs do not work though the classical estrogen receptor, however the drug is termed according to this classical model.

We know estrogen has non-genomic effects that for example also induce nitric oxide. But these effects are still because of estrogen alpha interacting with other proteins (I mean the induction of NO. The effects on the structure of water are ER indepedant, but this is irrelevant in this context). These drugs may inhibit NO synthesis and therefore you expect (not tested) higher INF, and this may play a possible role in vivo. However cell lines expressing low to no estrogen receptor also get infected easily..

Mmmhh...? Sure these data on ER expression may be underrated. But, from this study, I absolutely don't think it's that clear that it is all estrogen and not some other properties of these drugs. (drugs do a lot). See below what the study itself come up with. I think this is more likely to be honest.

The ER antagonist drugs identified in our screen—clomiphene, toremifene, tamoxifen, and raloxifene—are structurally similar (5) and can be classified as class II cationic amphiphiles (CADs). CADs contain a hydrophobic tertiary amine with clearly segregated hydrophobic and hydrophilic segments. Our results here along with other studies indicate that CADs inhibit EBOV entry (26, 32).

In further support of clomiphene and toremifene interfering with filoviral fusion, we have observed that higher concentrations of clomiphene and the other CADs are required for inhibition in EBOV pseudovirus infection studies in cells overexpressing the EBOV entry factor NPC1, compared to parental cells (32). These results support a mechanism where clomiphene and other CADs mediate EBOV inhibition at a later step in the entry process.

EDIT: hopefully my thoughts are somewhat less confusing now.

 

[LucyL]

How do you define estrogen antagonists?

The study that finds these drugs to be helpful, also says that these drugs do not work though the classical estrogen receptor, however the drug is termed according to this classical model.

......

Mmmhh...? Sure these data on ER expression may be underrated. But, from this study, I absolutely don't think it's that clear that it is all estrogen and not some other properties of these drugs. (drugs do a lot). See below what the study itself come up with. I think this is more likely to be honest.

Here is the link to the study FDA-Approved Selective Estrogen Receptor Modulators Inhibit Ebola Virus Infection

Perhaps what is really needed is to define "estrogen receptors". From the study:

Anti-EBOV activity was confirmed for both of these SERMs in an in vivo mouse infection model. This anti-EBOV activity occurred even in the absence of detectable estrogen receptor expression, and both SERMs inhibited virus entry after internalization, suggesting that clomiphene and toremifene are not working through classical pathways associated with the estrogen receptor.

In Ray's newsletter on estrogen receptors, he wrote that they (the proteins so identified) were basically a property of normal tissue, and the absence of an "estrogen receptor" is an indication that tissue is abnormal. But generally, Ray doesn't buy the theory of estrogen receptors at all, he says "Estrogen produces many effects without the "receptor".

Chlomiphene is considered a rather potent anti-estrogen drug, it interrupts estrogen feedback to the hypothalmus.

In Estrogen and brain aging... Ray writes:

Estrogen activates the adrenal stress reaction by way of the hypothalamus and pituitary, by direct actions on the adrenal glands, and by a variety of indirect effects, such as the increase of free fatty acids. It activates the excitotoxic glutamic acid pathway, and interferes with protective adenosine inhibition of nerves. It has both direct and indirect ways of promoting the formation of nitric oxide and carbon monoxide. These, and other estrogen-promoted factors, quickly and seriously interfere with mitochondrial respiration. Many of these effects contribute to increased intracellular calcium and free radical production, contributing to both the excitatory excess and the energy deficit.

So much to consider.

 

[Suikerbuik]

So much to consider.

Yeah absolutely.

what I find strange is that estrogen agonists. However at lower maximal effects (41-54%) also lower ebola infection..??

According to protein atlas, some tissue really do not have estrogen receptive proteins. But like I said maybe this is underrated.. I think it could depend on the context too. With reservation I thought Ray said this is in context of breast cancer tissue?