Introduction to how viruses work and Antivirals

Discussion in 'Fibromyalgia Main Forum' started by karinaxx, Nov 18, 2006.

  1. karinaxx

    karinaxx New Member

    a while ago i found this fantastic site and since there are so many people trying out Antivirals, i thought i share this site with you.
    it is realy simple, just right for our CFIDS brains and is actually a site for students.

    here is a sample; the info on viruses is several pages and with ilustrations.
    if you want get the whole information on viruses and other stuff, check out the site:
    http://health.howstuffworks.com/virus-human.htm

    What is a Virus?
    If you have read How Cells Work, you know how both bacteria cells and the cells in your body work. A cell is a stand-alone living entity able to eat, grow and reproduce. Viruses are nothing like that. If you could look at a virus, you would see that a virus is a tiny particle. Virus particles are about one-millionth of an inch (17 to 300 nanometers) long. Viruses are about a thousand times smaller than bacteria, and bacteria are much smaller than most human cells. Viruses are so small that most cannot be seen with a light microscope, but must be observed with an electron microscope.
    A virus particle, or virion, consists of the following:

    Nucleic acid - Set of genetic instructions, either DNA or RNA, either single-stranded or double-stranded (see How Cells Work for details on DNA and RNA)
    Coat of protein - Surrounds the DNA or RNA to protect it
    Lipid membrane - Surrounds the protein coat (found only in some viruses, including influenza; these types of viruses are called enveloped viruses as opposed to naked viruses)
    Viruses vary widely in their shape and complexity. Some look like round popcorn balls, while others have a complicated shape that looks like a spider or the Apollo lunar lander.
    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. So, a virus must have a host cell (bacteria, plant or animal) in which to live and make more viruses. Outside of a host cell, viruses cannot function. For this reason, viruses tread the fine line that separates living things from nonliving things. Most scientists agree that viruses are alive because of what happens when they infect a host cell.

    to be continued........... on their site

    for never ending education
    karina

    [This Message was Edited on 11/28/2006]
  2. sascha

    sascha Member

    concept of a virus. i really need that simplification as it's hard to keep complicated information straight.

    i am going to check out that web site. Sascha
  3. karinaxx

    karinaxx New Member

    i know what you mean.
    karina
  4. cct

    cct Member

    bumping for others to read
  5. Scapper

    Scapper New Member

    Thanks so much for this information :)

    SCAPPER
  6. Mikie

    Mikie Moderator

    And it's simply called, "Viruses." It's very good at explaining the various kinds of viruses and the illnesses they cause.

    There is a lot of info on viruses on the web if you do a search. A search on stealth viruses will bring up a lot of info on HHV-6. It is one of the most virulent viruses yet encountered and very difficult to treat. There is a book about it called, "The Virus Within." It's an excellent read and resource.

    Love, Mikie
  7. karinaxx

    karinaxx New Member

    thanks for you info on book.

    i take my info on viruses from different sources and this was just a small and short info, as a easy start getting into the theme.

    i prefere actually the internet for more up to date infos. one very good source is Wikipedia, the free encyclopedia.htm type in search on cfids or cfs, or post polio and much more, you will find truly AHA moments.

    for up to date infos on hhv-6, i would advise to check out the foundation http://www.hhv-6foundation.org/.
    there has been a lot of new research done in connection with MS and HHV-6, and if you google you find a lot of very intersting stuff on that too.


    EVERYONE HERE SHOULD NOT TAKE MY WORD OR YOURS FOR INFORMATION, check out as many different infos as you can and make up there own mind!!!! !!!!!!!!

    karina

    Antiviral drug
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    This article has been tagged since June 2006.
    Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics, specific antivirals are used for specific viruses. Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotics, anti-fungal and anti-parasitic drugs. They are relatively harmless to the host, and therefore can be used to treat infections. They should be distingushed from viricides, which actively deactivate virus particles outside the body.

    Most of the antivirals now available are designed to help deal with HIV, herpesvirus, which is best known for causing cold sores but actually covers a wide range of diseases, and the hepatitis B and C viruses, which can cause liver cancer. Researchers are now working to extend the range of antivirals to other families of pathogens.

    The emergence of antivirals is the product of a greatly expanded knowledge of the genetic and molecular function of organisms, allowing biomedical researchers to understand the structure and function of viruses, major advances in the techniques for finding new drugs, and the intense pressure placed on the medical profession to deal with the human immunodeficiency virus (HIV), the cause of the deadly acquired immunodeficiency syndrome (AIDS) epidemic. Though no one could sensibly claim that AIDS has been a benefit to humankind, it has certainly done much to advance the state of antiviral technology.

    Contents
    [hide]
    1 History
    2 Development of antiviral drugs
    3 Antiviral drug design strategies
    4 See also



    [edit] History
    Modern medical science and practice has something of an armory of effective tools, ranging from antiseptics and anesthetics to vaccines and antibiotics. One field in which medicine has been traditionally weak, however, is in finding drugs to deal with viral infections. To be sure, highly effective vaccines have been developed to prevent such diseases, but traditionally, once somebody came down sick with a virus, there was little that could be done but recommend rest and plenty of fluids until the disease ran its course.

    The first experimental antivirals were developed in the 1960s, mostly to deal with herpesviruses, and were found using traditional trial-and-error drug discovery methods.

    Since the mid-1980s, that scenario has changed dramatically. Dozens of antiviral treatments are now available, and most medical researchers feel we are only scratching at the surface of what can be done with these new drugs.


    [edit] Development of antiviral drugs
    Viruses, not quite proper living things, consist of a genome and sometimes a few enzymes (biocatalysts) stored in a capsule made of protein, and very rarely covered with a lipid (fat) layer. Viruses cannot reproduce on their own, and so they propagate by hijacking cells to do the job for them.

    To develop early antivirals, researchers grew cultures of cells and infected them with the target virus. They then introduced chemicals into the cultures thought likely to inhibit viral activity, and observed whether the level of virus in the cultures rose or fell. Chemicals that seemed to have an effect were selected for closer study.

    This was a very time-consuming, hit-or-miss procedure, and in the absence of a good knowledge of how the target virus worked, not very good at discovering antivirals that were effective and had few side effects. It wasn't until the 1980s, when the full genetic sequences of viruses began to be unraveled, that researchers began to learn how viruses worked in detail, and exactly what kinds of molecules were needed to jam their machinery.

    The general idea behind modern antiviral drug design is to identify viral proteins, or parts of proteins, that can be disabled. These "targets" should generally be as unlike any proteins or parts of proteins in humans as possible, to reduce the likelihood of side effects. The targets should also be common across many strains of a virus, or even among different species of virus in the same family, so a single drug will have broad effectiveness. For example, a researcher might target a critical enzyme synthesized by the virus, but not the patient, that is common across strains, and see what can be done to interfere with its operation.

    Once targets are identified, candidate drugs can be selected, either from drugs already known to have appropriate effects, or by actually designing the candidate at the molecular level with a computer-aided design program.

    In either case, the candidates can be synthesized by plugging the gene that synthesizes that protein into bacteria or other kinds of cells. The bacteria or cells are then cultured for mass production of the protein, which can then be sifted by "rapid screening" technologies to see which of the candidates are the most effective.


    [edit] Antiviral drug design strategies
    Researchers working on such "rational drug design" strategies for developing antivirals have tried to attack viruses at every stage of their life cycles. Viral life cycles vary in their precise details depending on the species of virus, but they all share a general pattern:

    Attachment to a host cell.
    Release of viral genes and possibly enzymes into the host cell.
    Replication of viral components using host-cell machinery.
    Assembly of viral components into complete viral particles.
    Release of viral particles to infect new host cells.
    The best time to attack a virus is as early as possible in its life cycle. In a sense, this is exactly what vaccines do. Vaccines traditionally consist of a weakened or killed version of a pathogen, though more recently "subunit" vaccines have been devised that consist strictly of protein targets from the pathogen. They stimulate the immune system without doing serious harm to the host, and so when the real pathogen attacks the subject, the immune system responds to it quickly and blocks it.

    Vaccines have an excellent track record for effectiveness, but they are of limited use in treating a patient who has already been infected. That's where antiviral drugs come in.

    One approach is to interfere with the ability of a virus to get into a target cell. The virus has to take a sequence of actions to do this, beginning with binding to a specific "receptor" molecule on the surface of the host cell and ending with the virus "uncoating" inside the cell and releasing its payload. Viruses that have a lipid envelope must also fuse their envelope with the target cell, or with a vesicle that transports them into the cell, before they can uncoat.

    This stage of viral replication can be inhibited in two ways: 1. Using agents which mimic the virus-associated protein (VAP) and bind to the cellular receptors. This may include VAP Anti-idiotypic antibodies, anti-receptor antibodies, and natural ligands of the receptor and anti-receptor antibodies. 2. Using agents which mimic the receptor and bind to the VAP. This includes anti-VAP antibodies, receptor anti-idiotypic antibodies, extraneous receptor and synthetic receptor mimics.

    This strategy of designing drug can be very expensive. The process of generating anti-idiotypic antibodies is not fully understood. And it has very poor pharmacokinetics.

    A very early stage of viral infection is viral entry, when the virus attaches to and enters the host cell. A number of "entry-inhibiting" or "entry-blocking" drugs are being developed to fight HIV. HIV most heavily targets the immune-system white blood cells known as "helper T cells", and identifies these target cells through T-cell surface receptors designated "CD4" and "CCR5". Attempts to interfere with the binding of HIV with the CD4 receptor have failed to stop HIV from infecting helper T cells, but research continues on trying to interfere with the binding of HIV to the CCR5 receptor in hopes that will be more effective.

    However, two entry-blockers, amantadine and rimantadine, have been introduced to combat influenza, and researchers are working on entry-inhibiting drugs to combat hepatitis B and C virus.

    One entry-blocker is pleconaril. Pleconaril works against rhinoviruses, which cause the common cold, by blocking a pocket on the surface of the virus that controls the uncoating process. This pocket is similar in most strains of rhinoviruses and enteroviruses, which can cause diarrhea, meningitis, conjunctivitis, and encephalitis.

    A second approach is to target the processes that synthesize virus components after a virus invades a cell. One way of doing this is to develop "nucleotide or nucleoside analogues" that look like the building blocks of RNA or DNA, but jam the enzymes that synthesize the RNA or DNA once the analogue is incorporated.

    The first successful antiviral, aciclovir, is a nucleoside analogue, and is effective against herpesvirus infections. The first antiviral drug to be approved for treating HIV, zidovudine (AZT), is also a nucleoside analogue.

    An improved knowledge of the action of reverse transcriptase has led to better nucleoside analogues to treat HIV infections. One of these drugs, lamivudine, has been approved to treat hepatitis B, which uses reverse transcriptase as part of its replication process. Researchers have gone farther and developed inhibitors that do not look like nucleosides, but can still block reverse transcriptase.

    Other targets being considered for HIV antivirals include RNase H, which is a component of reverse transcriptase that splits the synthesized DNA from the original viral RNA; and integrase, which splices the synthesized DNA into the host cell genome.

    Once a virus genome becomes operational in a host cell, it then generates messenger RNA (mRNA) molecules that direct the synthesis of viral proteins. Production of mRNA is initiated by proteins known as transcription factors. Several antivirals are now being designed to block attachment of transcription factors to viral DNA.

    Genomics has not only helped find targets for many antivirals, it has provided the basis for an entirely new type of drug, based on "antisense" molecules. These are segments of DNA or RNA that are designed as "mirror images" to critical sections of viral genomes, and the binding of these antisense segments to these target sections blocks the operation of those genomes. A phosphorothioate antisense drug named fomivirsen has been introduced, used to treat opportunistic eye infections in AIDS patients caused by cytomegalovirus, and other antisense antivirals are in the works. An antisense structual type that has proven especially valuable in research is Morpholino antisense. Morpholino oligos have been used to experimentally suppress many viral types including caliciviruses [1], flaviviruses (including WNV [2] , Dengue [3] and HCV [4] ), and coronaviruses [5] and are currently in clinical development.

    Yet another devious antiviral technique inspired by genomics is a set of drugs based on ribozymes, which are enzymes that will cut apart viral RNA or DNA at selected sites. In the natural order of things, ribozymes are used as part of the viral manufacturing sequence, but these synthetic ribozymes are designed to cut RNA and DNA at sites that will disable them.

    A ribozyme antiviral to deal with hepatitis C is in field testing, and ribozyme antivirals are being developed to deal with HIV. An interesting variation of this idea is the use of genetically modified cells that can produce custom-tailored ribozymes. This is part of a broader effort to create genetically modified cells that can be injected into a host to attack pathogens by generating specialized proteins that block viral replication at various phases of the viral life cycle.

    Some viruses include an enzyme known as a protease that cuts apart viral protein chains so they can be assembled into their final configuration. HIV includes a protease, and so considerable research has been performed to find "protease inhibitors" to attack HIV at that phase of its life-cycle. Protease inhibitors became available in the 1990s and have proven effective, though they can have odd side-effects, for example causing fat to build up in unusual places. Improved protease inhibitors are now in development.

    The final stage in the life cycle of a virus is the release of completed viruses from the host cell, and this step has also been targeted by antiviral drug developers. Two drugs named zanamivir and oseltamivir that have been recently introduced to treat influenza prevent the release of viral particles by blocking a molecule named neuraminidase that is found on the surface of flu viruses, and also seems to be constant across a wide range of flu strains.

    A second category of tactics for fighting viruses involves encouraging the body's immune system to attack them, rather than attacking them directly. Some antivirals of this sort do not focus on a specific pathogen, instead stimulating the immune system to attack a range of pathogens.

    One of the best-known of this class of drugs are interferons, which inhibit viral synthesis in infected cells. One form of human interferon named "interferon alpha" is well-established as a treatment for hepatitis B and C, and other interferons are also being investigated as treatments for various diseases.

    A more specific approach is to synthesize antibodies, protein molecules that can bind to a pathogen and mark it for attack by other elements of the immune system. Once researchers identify a particular target on the pathogen, they can synthesize quantities of identical "monoclonal" antibodies to link up that target. A monoclonal drug is now being sold to help fight respiratory syncytial virus in babies, and another is being tested as a treatment for hepatitis B.

    Examination of the genomes of viruses and comparison with the human genome show that some are devious, generating proteins that mimic those used by the human immune system, confusing the immune-system response. Researchers are now hunting for antivirals that can recognize these intruder proteins and disable them.

    All drugs designed to fight pathogens have a common problem: over the long run, the pathogens evolve to acquire resistance to the drugs. This means that no antiviral will ever be a permanent solution. In fact, the structure of an antiviral compound will have to be tweaked as its target pathogen changes.

    This is the nature of the game. However, antivirals are now promising to be the biggest innovation in pharmaceuticals since the introduction of antibiotics during the Second World War, and promise to be a major step forward in health care.


    [edit] See also
    Antiretroviral drug
    List of antiviral drugs



    Antivirals (primarily J05A, also S01AD and D06BB) edit
    Anti-herpesvirus agents Aciclovir, Cidofovir, Docosanol, Famciclovir, Fomivirsen, Foscarnet, Ganciclovir, Idoxuridine, Penciclovir, Trifluridine, Tromantadine, Valaciclovir, Valganciclovir, Vidarabine
    Anti-influenza agents Amantadine, Oseltamivir, Peramivir, Rimantadine, Zanamivir

    Antiretroviral drugs NRTIs Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine, Zalcitabine, Zidovudine
    NtRTIs Tenofovir
    NNRTIs Efavirenz, Delavirdine, Nevirapine
    PIs Amprenavir, Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Nelfinavir, Ritonavir, Saquinavir, Tipranavir
    Fusion inhibitors Enfuvirtide

    Other antiviral agents Adefovir, Fomivirsen, Imiquimod, Inosine,Interferon, Podophyllotoxin, Ribavirin, Viramidine


    Retrieved from "http://en.wikipedia.org/wiki/Antiviral_drug"
    Categories: Cleanup from June 2006 | Antivirals



    This page was last modified 19:35, 28 September 2006.




    [This Message was Edited on 11/26/2006]
  8. Mikie

    Mikie Moderator

    This is soooo true. I think we each have to do our own research. Sharing what we find here is very helpful but nothing can replace individual research. I do not do as much of that as I used to. I do think the transfer factors have helped me more than anything when it comes to the tricky Herpes Family Viruses.

    The only problem I have with Wickipedia is that anyone can post info there, so you have to take it with a grain of salt. It's just like the info here; people need to use multiple sources of info and not rely on just one or two.

    Love, Mikie
  9. karinaxx

    karinaxx New Member

    your right about the wickipedia, of course recheck.
    i found that the site on cfids is very up to date and good.
    what i like is that it is updated regularly.

    transfer factor is indeed an interesting topic and i am glad it helped you so much.
    i am a bit hesitant, because the molecules are taken from animals....... i just speculate, but it could have long term some unknown side effects and with all this treatments, do they really adress the underlying issue???
    most of the treatments made me worse.....just more carefull now.

    take care
    karina
  10. mezombie

    mezombie Member

    I'm interested in treatments for reactivated viruses, which I seem to have. I went on Acyclovir years ago, definitely felt better, but lost the effect after about six weeks. I tried it again several years later, with divided doses taken throughout the day, but was never able to recapture what happened.

    Interestingly, I recently met with the very conservative infectious disease specialist who diagnosed me 15 years ago(but refused to treat me) He said he'd tried Acyclovir on some his patients as well, and the exact same thing happened.

    These viruses are clever! It's like they outsmarted the treatment. They become treatment-resistant very easily.

    I, too, am fascinated by Transfer Factor, but am dismayed at the small amount of research done on it. And, like Karinaxx, I'm concerned about side effects.

    If it really works, how does it work? The immune system is very complex, and it's easy to damage it without realizing it.

    Before I was diagnosed with CFS, I went through a year od not having a DX because I had a positive ANA and some other weird test results that could have been the start of Lupus. Throughout the 16 years I've been ill, these markers haven't changed.

    But at the time, I asked my rheumatologist about the immunemodulators on the market. He said he only prescribed them when absolutely necesssary, for diseases that could result in death if not treated.

    Because of the markers for autoimmunity I have (which do not correlate to any known disease), I'm concerned I could actually develop something worse than CFS if I played around with my immune system.

    I noticed, for example, that I would not be accepted for the open-label, cost-recovery Ampligen trial because of my positive ANA. And I recently listened to a presentation (found on the HemispherX website) on Ampligen given by one of the discovers. He, too, mentioned that no one knew if Ampligen might affect parts of the immune system negatively.

    If anyone knows of peer-reviewed research that would address my concerns, I would really appreciate it if you would let me know. Thanks!

    Zombie
    [This Message was Edited on 11/28/2006]
  11. karinaxx

    karinaxx New Member

    i will get back to you on this one.
    i am going through a hard time and have not energy to answer.
    i posted a link on the tranfer factor site, which is from the tranfer factor org.
    check if it is still there.

    karina
  12. karinaxx

    karinaxx New Member

    i replied to you short, but the message never made it.

    anyhow, i posted some infos on the transfer factor site, which gives some info on it.
    but one important link is gone. i will try to find it again. it is actually a research site of the transfer factor org.

    your ANA posititv is astonishing, but i would not give up finding out why. there are 60 diferent autoimmune deseases and some are very rare, so you Rheumy might just not know a few. the thing with autoimmune desesases is that they play ball in different fields, meaning that a rheumatologist will diagnose only a few, a neuro some few and so on.
    i researched this theme a bit, because i was, i am convinced that autoimmune clusters occur in CFIDS sufferes.
    here is one site, which list most of them http://www.aarda.org/patient_information.php
    another one is http://autoimmune.pathology.jhmi.edu/disease_systems.cfm

    just one question: at the time you were getting worse or discovered the ANA, did you have any treatment with Antibiotics?
    i found that some Antibiotics are actually inducing or exarborate preexisting Autoimmune deseases.
    One especially it the minocyclines, they can induce one kind of Lupus.

    i really i have to post all this stuff in connection with antibiotics and autoimmunety, just never got around to it.

    by karina




  13. Mikie

    Mikie Moderator

    May not be candidates for transfer factors because they increase the immune system's activity. Even though one can buy the TF's without prescription, I think it is vital to work with a doc before using them. I did. This was after tests to rule out autoimmunity.

    Colostrum and/or eggs are used in the production of TF's. There is a lot of info online about TF's if anyone is interested in researching them. I, personally, was not worried about these media used in the production of the TF's, but I can understand the concern.

    Love, Mikie
  14. karinaxx

    karinaxx New Member

    said.
    there are reports about Lupus patients using TFS and got a lot worse.
    i agree what Mickie says and thats exactly why i think it so important to do our own research on the treatments we consider, before we start anything.especially get to know the possible side effects they can have, so your able to recgonize and be able to make the difference between allergic ractions, sensitivetys,herxing and autoimmune reactions. i am speaking of experience!!!!! i had my share of troubles, i am still trying to recover from.

    and that includes Herbal stuff.
    Ecchinea for example is one, which can cause troubles in autoimmune patients and so on.

    karina
    [This Message was Edited on 11/29/2006]
  15. mezombie

    mezombie Member

    Karinaxx:

    Thank you so much for your concern and wise advise. And, of course, the websites! I'm having a very bad day, but will bookmark them and read later.

    No, I wasn't on antibiotics when the autoimmune stuff showed up. Interesting about all the different diseases out there it could be. I did get a second opinion from the Mayo clinic. They didn't think it was anything. Then again, the Mayo Clinic isn't what it used to be, if it ever was.

    I would never take Echinacea --- do NOT want to stimulate my immune system! Or anything else that will do that. I am very, very careful. It is much easier to make this DD worse than it is to make it better!

    Mikie:

    Thanks for your input. I totally agree with you that people should not go on any nutritional supplements or herbs without a doctor's supervision. I never have and never will. I'm not so sure that's true for many on this board.

    I think you do a superb job of gently reminding people to be careful of trying new products based solely on anecdotal evidence!

    To both of you:

    I'm just so sick, and sick of being sick! I read about the benefits people are getting from Transfer Factor, one of the few things I haven't tried, and was hoping my concern about it potentially stimulating the immune system was unfounded. Sigh. Oh well. Onward!
  16. fight4acure

    fight4acure Member

    Karina,

    Thanks, my biology class taught me this stuff, but it's always helpful to review.

    :)
  17. karinaxx

    karinaxx New Member

    but this time it was , i think , not intended by you.

    most of us here are over the age where you remember such stuff or at that time, there was not much known about it.
    so, i did not remember covering Antivirals in school!

    what school did you go tooooooo? medical school for todlers?????

    take care and by they way, i asked you in another post to keep us updated on you antiviral progress, what about it?
    love karina
  18. karinaxx

    karinaxx New Member

  19. Slayadragon

    Slayadragon New Member

    I like Wikipedia, because it is altered depending on comments by various people who write. It therefore has much more balanced and current information than most places about most topics.

    I'd never trust just one source, but Wikipedia seems like a goos starting point to me for most topics.