Wednesday, September 7, 2011

MIT Cures HIV?

Common Cold Virus
Sponsored by a grant from the National Institute of Allergy and Infectious Diseases and the New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases, with previous funding from the Defense Advanced Research Projects Agency, Defense Threat Reduction Agency, and Director of Defense Research & Engineering (now the Assistant Secretary of Defense for Research and Engineering), researchers at MIT may have found the cure for many viruses, including HIV. 


Hepatitis C
HIV
Fifteen viruses to be exact, including the cold virus (rhinovirus), strains of swine flu (H1N1 influenza), adenoviruses (which cause symptoms ranging from common cold syndrome to pneumonia, croup, and bronchitis), the dreaded stomach virus (reovirus), a polio virus, hepatitis C virus, dengue fever virus (breakbone fever), several members of hemorrhagic fever (arenavirus and bunyavirus), and highly lethal viruses such as Ebola or smallpox that might be used in bioterrorist attacks, hence the funding by the DoD.

MIT's new wonder drug (more virus warfare, or broad-spectrum antiviral approach, as they call it) is called DRACO (Double-stranded RNA [dsRNA] Activated Caspase Oligomerizer) and it was found to be nontoxic in 11 different cell types representing various species (e.g., humans, monkeys, mice) and organ types (e.g., heart, lung, liver, kidney). There have already been preliminary lab tests done on mice in which not only were they cured of a given virus but in some cases were saved from certain death; for example, when given a lethal dose of swine flu. In order to understand how the virus kryptonite DRACO works you must first understand a little about viruses and how they work. Get ready for a biochemistry and genetics crash course.

A virus is merely a set of genetic instructions, usually RNA, surrounded by a protein coat or envelope. All viruses have some type of protein on the outside coat that identifies a viable host cell. This protein attaches the virus to the membrane of the host cell. Some enveloped viruses can dissolve right through the cell membrane of the host because both the virus envelope and the cell membrane are made of lipids and because they do not carry out any biochemical reactions of its own, viruses can live for years or longer outside a host cell. Some viruses can "sleep" inside the genetic instructions of the host cells for years before reproducing. For example, a person infected with HIV can live without showing symptoms of AIDS for years, but they can still spread the virus to others.
Unlike human cells or bacteria, viruses do not contain the chemical machinery (enzymes) needed to carry out the chemical reactions for life. Instead, viruses carry only one or two enzymes that decode their genetic instructions. Therefore a virus must have a host cell in which to live and make more viruses. Outside of a host cell, viruses cannot function. Cold and flu viruses will attack cells that line the respiratory or digestive tracts. The human immunodeficiency virus (HIV), which causes AIDS, attacks the T-cells of the immune system.

I'm sure you already know the drill. You're at a crowded party and someone near you sneezes. You inhale a rhinovirus particle and it attaches to cells lining the sinuses in your nose. The virus attacks these cells and rapidly reproduces new viruses. The host cells break, and new viruses spread into your bloodstream and also into your lungs. Because you have lost cells lining your sinuses, fluid can flow into your nasal passages and give you a runny nose. Viruses in the fluid that drips down your throat attack the cells lining your throat and give you a sore throat. Viruses in your bloodstream can attack muscle cells and cause you to have muscle aches. Now you feel like you have the flu, but you are really in the grips of the common cold.




In computer terms a virus is a small bit of code that attaches itself to a program such as a spreadsheet. Each time the spreadsheet program runs, the virus runs too, and it has the chance to reproduce (by attaching to other programs). Biological viruses reproduce by transcription into viral mRNA (messenger RNA) molecules. RNA codons (basically the 1s and 0s that relate to the building blocks, amino acids) are read by your biological machinery and turned into polypeptides, or strings of amino acids, through a process called translation. Fold these polypeptides and you get proteins. As the host cell's ribosomes attach to the viral mRNA molecules, the mRNAs are translated into viral structural proteins and viral enzymes.

Essentially, DRACO is a protein with one part that binds to viral dsRNA (double stranded RNA) and a second domain that induces apoptosis, or cell suicide, when two or more DRACOs crosslink on the same dsRNA. If viral dsRNA is present inside a cell, DRACO will bind to the dsRNA and BAM! dead. If viral dsRNA is not present inside the cell, DRACO will not crosslink and everything stays rosey. DRACO works on the assumption that most viruses have double-(dsRNA) or single-stranded RNA (ssRNA) genomes and produce long (greater than ~21–23 base pairs) dsRNA helices during transcription and replication. Uninfected mammalian cells generally do not produce long dsRNA, so DRACO attacks cells that exhibit at least 30–50 base pairs. DRACO can be fused with proven protein transduction tags, including a sequence from the HIV TAT protein, the related protein transduction domain 4 (PTD), and polyarginine (ARG). These tags have been shown to carry large cargo molecules into both the cytoplasm and the nucleus of all cell types in vitro and in vivo, even across the blood-brain barrier. Because DRACO doesn't trigger within normal cells it rapidly heals a viral infection while minimizing side effects on the patient.

Ideally, you want the top left and bottom right images of each quad to be the same.

Clearly, this is a great step in Medicine even if the general public never sees it. I wonder, though, how they plan to administer said DRACO. I'm assuming by intramuscular injection, or a shot, which brings up the question, "How long will it take before all viruses are dead?" or asks the sick person, "How long before I feel better?"

Also, and I feel silly thinking it, but this reminds me of that movie I Am Legend in which most of the population becomes crazed and vampire-like after the world is unable to stop the spread of a virus, manufactured by man to cure cancer, mutates and spreads like wildfire. 

Plus, I don't think I can shoot Charlie when he becomes infected.



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