Will VTose work on this virus?

[rick]

With a broad-spectrum antiviral such as VTose, one of the most common questions we get is whether it will work on particular viruses.

The short answer is that we won't know for sure until we test. However, based on the known mechanism of action, we have a pretty good idea of how things should work.

In the original paper about DRACO, they tested against 15 different viruses, and found it was effective against all of them. Importantly, those tests included a wide range of different virus types. For example, positive and negative sense single-stranded RNA (ssRNA), double-stranded RNA (dsRNA) and DNA (dsDNA), with and without envelopes, replicating in the cytoplasm or the nucleus, in 11 different tissue types and with 7 different virus families:

The underlying mechanism of action involves latching onto long dsRNA segments, and then triggering apoptosis. Both of those functions, and the enzymes involved, are already naturally present in every human and animal cell. All we're doing is providing a shortcut that viruses shouldn't be able to bypass, as they often do.

As far as we know, all viruses create long dsRNA segments as part of their replication process. Based on that and the data in the table above, we have good reason to believe VTose may be effective against all human and animal viruses. However, having said that, there may be exceptions we aren't yet aware of.

One area of particular interest that wasn't previously tested is retroviruses, including HIV. Although they do still create dsRNA during viral replication, they also can "hibernate" in an inactive, dormant form. We have ideas about how to address this if it ends up being a problem, but it's something we will need to test.

[brittany]

What about HSV-1 & HSV-2? Will those also be tested?

[rick]

@brittany

What about HSV-1 & HSV-2? Will those also be tested?

Yes. HSV is definitely high in our queue of viruses of interest. In fact, we have already identified at least one lab that has both viruses and can do the testing.

Both HSV-1 and HSV-2 are dsDNA viruses with an envelope:

In addition to the human health concerns, that combination is one the previous research didn't test against, which further adds to our interest and motivation.

HSV is another case where the virus can be dormant or latent, although the way it works is different than with retroviruses, so it's interesting to test from that perspective, as well.

[rick]

A question has come up about whether VTose is likely to work against the HTLV virus (Human T-Lymphotropic Virus).

HTLV has been implicated as a cause of adult T-cell leukemia, HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-associated uveitis, and infective dermatitis. HTLV is usually transmitted from mother to child during breastfeeding.

HTLV is a retrovirus (the first retrovirus discovered), in the deltaretrovirus genus. It's an enveloped, (+)ssRNA virus.

The good news is that DRACO was tested and found effective against the Dengue virus, which is also an enveloped, (+)ssRNA virus -- as is SARS-CoV-2. On that basis, there's good reason to be optimistic that VTose will work against it.

Unfortunately, though, no testing has yet been done against retroviruses, which are different than other viruses in that they integrate a provirus into the cell's DNA, and can be latent, and replicate that way. It may be that it takes some time to clear viruses like that, since the dsRNA we need as a trigger may not appear until they go back to lytic replication.

[jim]

What strains of HPV are you testing on?  I’m curious about 6 and 11.  Thank you.

[rick]

@jim

What strains of HPV are you testing on? I’m curious about 6 and 11. Thank you.

HPV can be a bit challenging to test against, so we haven't made a definitive decision regarding strain yet. At the moment, one of the labs we're talking to does a lot of work with HPV16, so we may start there. Our expectation is that effectiveness shouldn't vary much from one strain to another, but that is, of course, something we will need to test.

[sdescon]

@rick

Unfortunately, though, no testing has yet been done against retroviruses, which are different than other viruses in that they integrate a provirus into the cell’s DNA, and can be latent, and replicate that way. It may be that it takes some time to clear viruses like that, since the dsRNA we need as a trigger may not appear until they go back to lytic replication.

Hopefully latent viruses like HIV and HSV can be counteracted by a combination of Vtose (for lytic infection), an LRA (Latency Reversing Agent)1, and a viral reseeding blocker (such as fusion and integrase inhibitors, N/NNRTIs, or protease inhibitors). The great thing is Vtose need not be used alone and will likely have synergism for the viruses we have other treatment for. Of course it will also be our very first way to fight the vast majority of other viral diseases where we have no treatments.

1. https://www.frontiersin.org/articles/10.3389/fmicb.2019.03060/full

[rick]

@sdescon

Hopefully latent viruses like HIV and HSV can be counteracted by a combination of Vtose (for lytic infection), an LRA (Latency Reversing Agent)1, and a viral reseeding blocker (such as fusion and integrase inhibitors, N/NNRTIs, or protease inhibitors). The great thing is Vtose need not be used alone and will likely have synergism for the viruses we have other treatment for. Of course it will also be our very first way to fight the vast majority of other viral diseases where we have no treatments.

Yes, exactly! We have a few other ideas along similar lines, too.