New Approaches in Anti-Viral Warfare: Hope for HIV, HepC, HSV ...?

Here are three promising new approaches to meeting the threat of the viral apocalypse:

1. Teach the body to throw a "monkey-wrench" into the virus assembly, preventing the virus from forming
2. Devise a "super-interferon" broad spectrum super-antiviral
3. Teach cells that are infected with dangerous viruses to commit suicide

Wired.co.uk

Buoyed by advances in molecular biology, a handful of researchers in labs around the US and Canada are homing in on strategies that could eliminate not just individual viruses, but any virus, wiping out viral infections with the same efficiency that penicillin and ciproflaxacin bring to the fight against bacteria. If these scientists succeed, future generations may struggle to imagine a time when we were at the mercy of viruses, just as we struggle to imagine a time before antibiotics.

Three teams in particular are zeroing in on new antiviral strategies, with each taking a different approach to the problem. But at root they are all targeting our own physiology, the aspects of our cell biology that allow viruses to take hold and reproduce. If even one of these approaches pans out, we might be able to eradicate any type of virus we want.

...The first thing researchers at Prosetta had to do was search for promising candidates -- molecules of just the right shape to lodge into the capsid-making machinery. They screened 80,000 compounds by testing each in a cell-free system. Most couldn't stop capsids from forming, but a few dozen did. Instead of focusing on one, Lingappa decided to pursue almost all of them on the premise that a victory against any one virus would help Prosetta extend its strategy to all of them.

It was a gutsy strategy, and so far it's paying off. Studies -- in both cell cultures and on animals -- are showing that Prosetta's approach can stop rabies, Ebola, influenza and a number of other viruses. If, as Lingappa suspects, all viruses need help from their host cells to assemble, he may have found a strategy that can work against every virus that could ever make us sick.

[The] second approach is being spearheaded by Eleanor Fish of the University of Toronto. She and other researchers worldwide are developing drugs that might replace or supplement interferons, our own catch-all viral response proteins. Essentially the idea is to accelerate the body's own virus-killing powers. Our cells can sense a viral invasion because of a quirk in the way most viruses replicate: using the host cell's machinery, they copy their own genes by making a peculiar molecule called double-stranded RNA. So our cells are equipped with proteins whose sole job is to detect double-stranded RNA. When they do, they relay a signal throughout the cell that an intruder has invaded.

The cell then produces interferons, which in turn trigger the production of more than 300 other kinds of proteins, each with its own role to play in killing viruses. Some slice up the virus's genes and wreck its proteins. Others tell the cell to become rigid, making it harder for new viruses to escape. The infected cell also sends interferons to surrounding cells, creating a firebreak that stops the spread of the infection. "The very first response to a virus is an interferon response," Fish says.

...By tacking on polyethylene glycol -- a cluster of hydrogen, carbon and oxygen atoms -- they've created synthetic interferons that last days instead of hours and will wipe out hepatitis C viruses completely in up to 81 per cent of treated patients, depending on the strain. During Toronto's Sars outbreak, Fish tested synthetic interferons on a small pool of patients and found that their lungs healed significantly faster than those of control patients, allowing them to get off supplemental oxygen sooner. Like Lingappa, Fish has huge ambitions for these synthetics. If one of them succeeds, it could become a single drug to fight not just one virus or a few, but nearly every virus.

...The third and arguably the most radical approach to broad-spectrum antivirals was conceived years ago by biological engineer Todd Rider... "I wanted a treatment that was broad spectrum, that was effective against a wide range of viruses, and that would be difficult for viruses to evolve resistance to," he says.

That something was an artificial protein. To make it, he would need to marry parts of two natural proteins. One string would detect double-stranded RNA, the telltale sign of most invading viruses. The other would lead the infected cell to kill itself. Rider wanted to make a poison pill for cells: a protein that, when it grabbed on to the double-stranded RNA of a virus, would trigger instant cellular suicide. That may sound like a dangerous kind of therapy, but our bodies already rely on it naturally to fight both infections and cancer.

Rider dubbed his theoretical molecule Draco, for double-stranded RNA activated caspase oligomeriser. _Wired

These approaches represent a departure, of sorts, from conventional consensus antiviral approaches. Sceptics of traditional approaches, scientific mavericks blaze new trails of discovery which their orthodox "safety in the crowd" colleagues would never risk.

The fact that it has taken so long for humans to begin to devise such strategies, in the face of desperate need, suggests that human educators and human societies are not raising children who can make use of their innate intellects and creativity. The brains that we have are being wasted, and the brains that we could have are not imagined or conceived. The intellectual powers we do have are too often squandered on consensual orthodoxies, intellectual treadmills to nowhere.

MIT Scientists Unleash DRACO: Viral Genocide Imminent

We have developed a new broad-spectrum antiviral approach, dubbed Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO) that selectively induces apoptosis in cells containing viral dsRNA, rapidly killing infected cells without harming uninfected cells. We have created DRACOs and shown that they are nontoxic in 11 mammalian cell types and effective against 15 different viruses, including dengue flavivirus, Amapari and Tacaribe arenaviruses, Guama bunyavirus, and H1N1 influenza. _PLoS

PLoS One: Broad Spectrum Anti-viral
The DRACO antiviral approach created by MIT researchers has the potential to develop into an all-purpose antiviral prophylactic and early-stage treatment. This development is a timely reminder that while microbes can be shifty and clever in avoiding antimicrobial medicines, humans have incredibly creative and resourceful brains -- if they would only use them.

Now, in a development that could transform how viral infections are treated, a team of researchers at MIT’s Lincoln Laboratory has designed a drug that can identify cells that have been infected by any type of virus, then kill those cells to terminate the infection.

In a paper published July 27 in the journal PLoS One, the researchers tested their drug against 15 viruses, and found it was effective against all of them — including rhinoviruses that cause the common cold, H1N1 influenza, a stomach virus, a polio virus, dengue fever and several other types of hemorrhagic fever.

The drug works by targeting a type of RNA produced only in cells that have been infected by viruses. “In theory, it should work against all viruses,” says Todd Rider, a senior staff scientist in Lincoln Laboratory’s Chemical, Biological, and Nanoscale Technologies Group who invented the new technology.

Because the technology is so broad-spectrum, it could potentially also be used to combat outbreaks of new viruses, such as the 2003 SARS (severe acute respiratory syndrome) outbreak, Rider says.

...When viruses infect a cell, they take over its cellular machinery for their own purpose — that is, creating more copies of the virus. During this process, the viruses create long strings of double-stranded RNA (dsRNA), which is not found in human or other animal cells.

As part of their natural defenses against viral infection, human cells have proteins that latch onto dsRNA, setting off a cascade of reactions that prevents the virus from replicating itself. However, many viruses can outsmart that system by blocking one of the steps further down the cascade.

Rider had the idea to combine a dsRNA-binding protein with another protein that induces cells to undergo apoptosis (programmed cell suicide) — launched, for example, when a cell determines it is en route to becoming cancerous. Therefore, when one end of the DRACO binds to dsRNA, it signals the other end of the DRACO to initiate cell suicide.

Combining those two elements is a “great idea” and a very novel approach, says Karla Kirkegaard, professor of microbiology and immunology at Stanford University. “Viruses are pretty good at developing resistance to things we try against them, but in this case, it’s hard to think of a simple pathway to drug resistance,” she says.

Each DRACO also includes a “delivery tag,” taken from naturally occurring proteins, that allows it to cross cell membranes and enter any human or animal cell. However, if no dsRNA is present, DRACO leaves the cell unharmed.

Most of the tests reported in this study were done in human and animal cells cultured in the lab, but the researchers also tested DRACO in mice infected with the H1N1 influenza virus. When mice were treated with DRACO, they were completely cured of the infection. The tests also showed that DRACO itself is not toxic to mice. _Physorg

So far, the treatment appears safe and non-toxic, and fairly effective when used pre-infection, and in the early stages of infection, for the viruses tested. Whether this general approach will lead to successful treatments for herpes viruses or HIV and other retroviruses, remains to be studied.

Since DRACO leads to the death of viral-infected cells, the potential exists that this approach might lead to eradication of "stealth viruses" which hide in particular cell types for a person's entire lifetime.

As for other stealth viruses living inside human cells which have not been discovered by human science, presumably some of these would also be killed by a DRACO-like approach. No one knows what the result of such a broad-spectrum clearance of body viruses might be, because no one knows what these undiscovered stealth viruses are doing in the first place. Assuming they are there, which is quite probable, according to Al Fin system biologists.

Snowcrash' Carnival of Biosingularity

This excellent video on retroviral mechanisms is just one of a wonderful carnival of 4th of July postings from our old friend Snowcrash at Biosingularity. Check them out.

200 X Better than Tamiflu Against H5N1 Avian Flu?

In vitro activities of AviFluCide, specific to H5N1, and of FluCide, lead us to suggest that AviFluCide could be as much as 100-200X (10,000% to 20,000%) more efficacious in H5N1 avian influenza treatment than oseltamivir. Nanoviricides are being constructed against Rabies, Dengue virus and Hepatitis C virus. Our technology also enables the possibility of stockpiling one drug that can specifically attack a number of pathogens. Additionally, nanoviricides open up an interesting new approach to epidemic threat containment. Theoretically, a nanoviricide can be constructed against a field pathogen using antibody fragments as ligands, leading to the fastest possible response to a natural epidemic or bioterrorism threat.

At the recent Nanotech 2007 Conference in Santa Clara, the president of Nanoviricides unveiled an electron microcraph showing the destruction of murine CMV by a nanoviricide. Here is an abstract of the presentation.

Although Tamiflu is a relatively old antiviral drug, it is currently seen as the best defense against an avian flu outbreak/pandemic in humans.

Nanomedicine offers the ability to approach age-old medical problems from a fresh perspective. Nanotechnology opens the door to the perspectives of workers from several disciplines that contribute to nanomedical principles.

Although large pharmaceutical companies tend to fall into the type of unimaginative ruts that plague all large organisations, the ability of small focused startups in biotech and nanotech medicine allow the constant infusion of new ideas and techniques into the larger field of pharmacology and pharma-therapy.

This type of startup activity feeding into larger pre-existing industry is only possible in a culture that values independence of thought and action. Such a culture tolerates the inevitable risk that accompanies startups--venture capital, entrepreneurial risk, etc.

Such revolutionary activity could not occur so freely in cultures that value security over all else. That is why so many cutting-edge researchers tend to migrate away from nanny/security cultures to more open opportunity cultures.