Anti-Viral Drugs Flashcards
What are viruses?
small infective agents consistening of nucleic acid (RNA or DNA) enclosed in a protein coat.
They are not cells as they have no metabolic machinery of their own; obligate intracellular parasites
What viruses contain double stranded DNA?
- Herpes virus
- poxvirus
- adenovirus
- hepadnavirus
What viruses contain single stranded DNA?
- parvovirus
What viruses contain positive single stranded RNA?
- piconaviridae
- calicivirus
- togavirus and flavivirus
- coronavirus
What viruses contain negtaive single stranded RNA?
- Paramyxoviridaw
- Orthomyxoviridae
- Arenvirus
- Rhabdovir dae
What viruses contain positive ssRNA that is converted to DNA?
retroviruses
What viruses are common in the brain?
- HSV
- rabies
- picronaviruses
- HIV
- measles
- mumps
- toga
- falvi
- encephalitis viruses (tropical diseases)
What viruses are common in the eyes?
- HSV
- adenovirus
- measles
What viruses are common in the nose?
- Common cold
- rhinovirus
- influenzas
- coronavirus
- RSV
- adenovirus
- parainfluenza
- Pharyngitis
- adenovirus
- HSV
- EBV
- coxachie virus
- Lower respiratory
- influenza
- parainfluenza
- RSV
- adenovirus
What viruses are common in the enteric system (intestines)?
- rotavirus
- Norwalk
- Adenovirus
- picornaviruses
What viruses are common in the urogenital system?
- HSV
- papilloma
What viruses are common in the lymphoid system?
- EBV
- CMV
What viruses are common in the liver?
- hepatitis
- yellow fever
- CMV
- EBV
What viruses are common in the heart?
- coxachie virus
What viruses are common in the skin and mucous membranes
- HSV
- VZV
- measles
- rubella
- papilloma
- B19 parvorius
What viruses are common in the mouth?
HSV and coxachie virus
Describe viral replication
- viruses have no metabolic machinery
- attach to and enter a living host cell-animal. Binding sites on the virus are polypeptides in the envelope or caspid
- virus attaches to normal receptors on the host cell and enters the cell by endocytosis or another by pass route
- once in the host cell the nucelic acid of the virus then uses the cell’s machinery for synthesising nucleic acid and protein and the manufacture of the new virus particles
What are the 9 processes in the virus life cycle that can be targeted by anti-viral drugs?
- recognition
- attachment
- fusion and penetration
- uncoating
- transciption
- protein synthesis
- replication
- assembly
- lysis/budding and release
How do nucleoside/nucelotide analogues work?
They are compounds with a very similar structure to human nucelotides so act by taking the place of standard nucelotides we use to build DNA
This means they block the building/synthesis of the DNA chain
What are the two types of reverse transciptase inhibitors? And how many in each category are approved for use?
- Nuceloside analogues (NRTIs) = 8
- Non-nuceloside anagloues (NNRTIs) = 4
How does a NRTI work?
inhibit viral DNA synthesis by acting as a chain termination
How does a NNRTI work?
Binding induces a conformational change that inhibit the catalytic activity of reverse transcriptase
What are the main NRTIs?
- abacavir
- didanosine
- emtricitabine
- stavudine
- lamivudine
- tenofovir
- zalcitabine
- zidovudine
What are the main NNRTIs?
- delavirdine
- efavirenz
- etravirine
- nevirapine
What are the 2 main protease inhibitors avalible for use in treating HCV?
- Telaprevir
- Boceprevir
What are the 2 main DNA viruses?
- herpes simplex virus (HSV)
- Human papilloma virus (HPV)
What is the general mechanism of DNA viruses?
- entry of the viral DNA into the host cells nucleus
- transciprtion of this viral DNA into mRNA by the hosy cell RNA polymerase
- followed by translation of the mRNA into virus-specific proteins
What drug is used in the treatment of herpres sumplex virus and varicella zoster virus?
Aciclovir
What are the main uses of aciclovir?
- genital herpes simplex
- herpes simplex lavialis (cold sores)
- shingles
- acute chicken pox in immunocompromised patients
- herpes simplex encephalitis
- Acute mucocutaneous HSV infections in immunocompromised patients
- herpes of the eye and herpes simplex blepharitis (eye)
What is not reduced by aciclovir?
PAIN
What are the other main drugs that can be used to treat herpes? And what is the main indication for these drugs?
- valaciclovir = a prodrug with better oral availability
- CMV: aciclovir not as active
Indication = compromised patients
What are the main RNA viruses?
Influenza (Flu), Hepatitis C Virus (HCV)
What are RNA viruses classified by?
according to the sense or polarity of their RNA
What is positive-sense RNA?
similar to mRNA and can be immediately translated by the host cell
What is negative sense RNA?
is complementary to mRNA and must be converted to positive-sense by an RNA polymerase before translation.
What directs the synthesis of more viral genomic RNA?
RNA polymerase
Where does virus replication of RNA viruses usually occur?
Cytoplasm
What are the main retroviruses?
HIV, Human T cell leukaemia virus (HTLV)
What is the action of retroviruses?
- virus contains reverse transcriptase and RNA-dependent DNA polymerase, which makes a DNA copy of the viral RNA
- DNA copy is intergrated into the genome of the host cell and is called a provirus
- provirus DNA is transcribed into both new genomic RNA and mRNA for translation into viral proteins using host cell machinery
What is zidovudine (AZT) an analogue of?
thymidine
What is abacavir (ABC) an analogue of?
guanosine
What is lamivudine (3TC) an analogue of?
cytosine
What is didanosine (ddl) an analogue of?
deoxyadenosine
What is zalcitabine (ddC) an analogue of?
cytosine
What is stavudine (d4T) an analogue of?
thymidine
How do nucleoside/nucelotide analogues work as anti-viral drugs?
- compete with natural substrate in DNA or RNA polymerisation
- Act as chain terminators by not offerinf the 3’-hydroxyl function, which is a requirement for incoming nucelotide binding
What do prodrugs require?
intracellular phosphorylation by viral and/or cellular kinases to cinvert them from 5’-monophosphate form to the 5’-triphosphate
How do protease inhibitors prevent viral replication?
- most mRNAs code directly from their functional proteins
- mRNA is translated into biochemically inert proteins
- A virus specific protease then coverts them into functional proteins
- A protease inhibitor simply prevents this process from occuring
What are the main protease inhibitors?
- amprenavir
- atazanavir
- darunavir
- fosamprebavir
- indinavir
- lopinavir
- nelfinavir
- ritonavir
- saquinavir
- tipanavir
What 2 reactions does HIV integrase madiate
3’ end processing of the double-stranded viral DNA ends and then strand transfer which joins the viral DNA to the host chromosomal DNA forming a functionally integrated provirus.
What are the main intergrase inhibitors?
- raltegravir
- dolutegravir
- Used in concurrent HAARt therapy
What is the action of fusion inhibitors?
Entry of HIV into a new cell is mediated by the Env glycoprotein spike a trimer of gp120 and gp41. Entry requires the receptor CD4 plus one of two co-receptors, CCR5 or CXCR4.
Example of a fusion inhibitor
Maraviroc
Enfurviritide
What is HAART?
Highly active antiretroviral therapy
What is atripla
2 NTRIs
1 NNRTI
Low cost fixed generic dosw
What are the main inhibitors of attachement to or penetration of host cells?
Amantadine and rimatadine
What is the mechanism of Amantadine & Rimantadine
At two stages of viral replication within the host cell, a viral membrane protein, M2, functions as an ion channel. The stages are (i) the fusion of viral membrane and endosome membrane and (ii) the later stage of assembly and release of new virions at the host cell surface. Amantadine blocks this ion channel.
What type of drugs are Amantadine & Rimantadine
M2 ion channel inhibitors
What are the main influenza inhibitors? and what is their mechanism of action
Tamiflu and Relenza
Neuraminidase (NA) inhibitors
How does neuraminidase work in influenza?
functions in Influenza infection by cleaving sialic acid from the cell surface so that newly made viruses are released and able to spread to uninfected cells.
NA inhibitors mimic the sialic acid natural substrate by binding to the NA active site, preventing NA function and hence halting virus replication.
What drugs are used in the treatment of hepatitis C?
- Ribavirin
- Peginterferon alpha
- Simeprevir Ledipasvir and sofosbuvir
• Protease inhibitors (grazoprevir, glecaprevir paritaprevir)
What is Immunomodulator PEG-IFN-α used in the treatment of?
HCV and HBV
