Medicines And Drugs 24.2 Antivirals

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Viruses

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Acellular parasites that replicate inside living cells

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Envelope

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membrane-like, sometimes surround viruses

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Most familiar retrovirus

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HIV (AIDS)

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Where does HIV reproduce?

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Inside a group of specialized white cells (T4 lymphocytes/T4 helper cells)

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anatomy of viruses

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DNA, protein capsule, sometimes envelope

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diseases caused by viruses

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consist of a nucleic acid surrounded by a protein capsid and sometimes a membrane-like envelope

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Familiar animal diseases caused by viruses:

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warts, herpes, meningitis, measles, influenza, rabies, hepaitis B, SARS, avian flu, and AIDS

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nucleic acid in viruses

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DNA, usually double-stranded, or RNA, usually single-stranded

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reverse transcriptase

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a viral enzyme that produces a DNA copy of the RNA (used in retroviruses, like HIV)

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HIV production

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reproduces inside white blood cells (T4 lymphcytes and T4 helper cells), which regulate the immune system

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why are retrouviruses unusual

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because their genetic information is in the form of two single-stranded RNA molecules

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Appearance of HIV virus

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spherical enveloppe of lipid bilayer with glycoproteins, protein coat, two strands of single stranded RNA, protein + enzyme

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How does HIV reproduce?

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Once inside the T4 lymphocyte, reverse transcriptase (enzyme in HIV) produces a DNA copy of the virus' RNA, which is then inserted into the DNA of the T4 lymphocyte

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process of reproduction of HIV

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binds, fusion of capule with cell membrane, enters lymphocyte, RNA-DNA-protein synthesis

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bacteria

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protective outer membrane, inner plasma membrane that encloses the cytoplams and nucleoid (the area of the cytoplasm that containts a single circular DNA molecule)

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peptidoglycans

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between inner and outer membranes, thin but strong layer of sugar polymers cross-linked by amino acids

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nucleoid

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area of cytoplasm that contains a single circular strand of DNA

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antimetabolite concept

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involves synthesis of modified chemical bases used in the synthesis of nucleic acid

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Virus outside of a cell

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state of suspended animation; cannot be targeted by drugs

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Virus inside the cell

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Incorporated into the host; hard to kill virus without killing the host

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outside cell, viruses

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cannot be targeted by drugs because they are in a state of suspended animation

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inside cell, viruses

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are incorporated into the host - therefore difficult to kill virus without killing cell

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bacteria

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protective outter membrane, inner plasma membrane,

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example of antimetabolite concpet drug

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zidovudine (retrovir or AZT)

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Tamiflu

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antiviral drug that is used in the treatment of influenza A and B infections

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Bacteria structure

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outer membrane, inner plasma membrane, thin but strong layer of sugar polymers cross-linked by amino acids between two membranes, single circular DNA molecule, flagella

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viral life cycle

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1. adsorption of the virus onto the cell surface, often onto specific receptor proetins 2. penetration, usually via engulfment of the virus particle by a small portion of the cell membrane during exocytosis 3. shedding of the protective protein capsid (enzyme-controlled process) 4. synthesis of viral proteins and viral nucleic acids

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HIV-1 Protease

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Enzyme for virus production

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Process of a viral cell infection

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1. Virus attaches to cell with help of binding protein 2. binding leads to fusion of capsule with cell membrane 3. Virus enters the lymphocte 4. HIV becomes part of the white cell's genome

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AIDS stigma

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discrimination, rejection, avoidance, violenve, quarantine

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only clinically available drugs against HIV

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nuceloside-based inhibitors of the viral enzyme reverse transcriptase such as AZT

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neuraminidase

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enzyme on the surface of influenza viruses that enables the virus to be released from the host cell

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how Tamiflu functions

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by inhibiting the viral enzytme neuraminidase

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why cant the viruses outside the cell be targeted by the drugs

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viruses are in a state of suspended animation and so it cannot be targeted by drugs

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nucleoid

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genetic material - a singular chromosome of about 4000 genes

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cell wall

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protects cells from rupture caused by osmosis and possible harm from other organisms

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Plasma membrane

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barrier across which all nutrients and waste producst must pass

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Forms of AIDS stigma

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discrimination, rejection, avoidance, violence and quarintine against and on HIV positive individuals, compulsory HIV testing without consent

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first step of viral infection

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absorbtion of virus onto the cell surface - no drugs available to prevent absorbtion

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Second step viral infection

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penetration; engulvment of the virus particle by a small portion of the cell membrane during exocytosis

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HIV

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undergoes mutations, new strains become increasingly resistant to drugs

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drugs to combat viral penetration

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amantadime prevents the release and uncoating of viruses- treats rubella

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Amantadine

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prevent release and uncoating of virusses and has been used to treat rubella (measles) and influenza (flu)

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chloroquine

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inhibits the uncoating of a virus - example Newcastle diease virus

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drug development in HIV-1 protease area

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1. production of peptide-based inihbitors of HIV protease that mimic the transition of state of the enzyme's substrate 2. synthesizing small non-peptide molecules that are able to bind to the active site of the protease

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Most promising point of attack for antiviral

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during the synthesis of viral proteins and viral nucleic acids

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Vaccines

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stimulate body's natural defences to produce antibodies against the virus

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antimetabolic concept

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sythesis of modified chemial bases used in the synthesis of nucleic acids example - zidovudine

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Antiviral drugs

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work in a number of ways: some alter the cell's genetic material, others inhibit the activity of enzymes or prevent viruses from binding to the host cell surface

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nucleotide- based inhibitors example AZT

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inhibits reverse transcriptase

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Phosphonoformic and phosphonoacetic acids

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two antiviral agents that inhibit the action of the viral DNA polymerase (which is responsible for the production DNA)

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second possible point of attack for antiviral drugs

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penetration, usually via engulfment of the viruses onto cell membranes

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AIDS and HIV treatment

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currently no vaccine or cure - antiretroviral treatment prolongs lives of people with HIV (but expensive and not avaiable in all countries)

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people living with HIV

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95% living in developing countries, <8% needing retroviral therapy recieve it

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slow spread of HIV

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abstinence campaigns, use of condoms, education & information

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Anti-metabolic concept

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synthesis of modified chemical bases used in synthesis of modified nucleic acids

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Example of a drug using the anti-metabolic concept

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zidovudine (AZT), is one of the few drugs with some success in the clinical treatment of AIDS.

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How does AZT work

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Once incorperated into growing DNA strands it causes termination and the reverse transcriptase can't extend the DNA chain anymore

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two approaches to drug development in HIV cure

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1: production of peptide-based inhibitors of HIV protease that mimic the transition state of the enzyme's substrate 2: synthesizing small non-peptide molecules that are able to bind to the active site of the protease

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AIDS stigma

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discrimination, rejection and avoidance of HIV-infected people, compulsory HIV testing w/o prior consent or protection of confidentiality, violence against HIV-infected individuals and quarantine of HIV-infected individuals; in some countries, association between AIDS and homosexuality or bisexuality - correlated with homphobia

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homosexuality

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some evidence that it is inherited an influnced