Chapter 20 Flashcards
____ are: an infective agent
typically consists of a nucleic acid molecule in a protein coat
too small to be seen by light microscopy
able to multiply only within the living cells of a host
Viruses
What are types of viral diseases?
common cold flu (influenza) herpes human immunodeficiency virus (HIV/AIDS) human papillomavirus (HPV) mumps, measles and rubella viral pneumonia
viral nucleic acid is covered by a protein coat of repeating units called?
capsids
either icosahedral (spherical) or helical symmetry
repeating units reduce the number of genes devoted to production of the viral coat and simplify the process of viral assembly
What are the 5 stages of the life cyle of viruses?
Adsorption: a virion has to first bind to the outer surface of a host cell. This involves a specific molecule on the outer surface of the virion binding to a specific protein or carbohydrate present in the host cell membrane.
Penetration and uncoating: different viruses introduce their nucleic acid into the host cell by different methods. Some inject their nucleic acid through the cell membrane; others enter the cell intact and are then uncoated.
Replication and transcription: viral genes can be defined as early or late. Early genes take over the host cell so that viral DNA and/or RNA can be synthesized.
Synthesis and assembly of nucleocapsids: late genes direct the synthesis of capsid proteins and these self-assemble to form the capsid.
Virion release: naked virions are released by cell lysis while viruses with envelopes are usually released by budding from host cell
What are the 4 general principles for good drug protein targets for viruses?
They are important to the life cycle of the virus such that their inhibition or disruption has a major effect on infection.
They bear little resemblance to human proteins, thus increasing the chances of good selectivity and minimal side effects.
They are common to a variety of different viruses and have a specific region which is identical in its amino acid composition. This makes the chances of developing a drug with broad antiviral activity more likely.
They are important to the early stages of the viral life cycle, which means that their disruption/inhibition reduces the chances of symptoms and of the virus spreading through the body
True or False: Most of the drugs which are active against DNA viruses have been developed against herpesviruses
True,
cold sores, genital herpes, chicken pox, shingles, eye diseases, mononucleosis, Burkitt’s lymphoma, Kaposi’s sarcoma
aciclovir has a nucleoside-like structure and contains the same nucleic acid base as deoxyguanosine (nucleoside primarily effective)
inhibitors of tubulin polymerization and have been used to treat genital warts caused by ______
papillomavirus
_____ was used to treat cytomegalovirus (CMV)(antisense therapy)
formivirsen
What activates aciclovir (nucleoside)?
Triphosphate
HIV drugs are grouped into five drug classes
nucleoside reverse transcriptase inhibitors (NRTIs)
- also includes a few nucleotide reverse
transcriptase inhibitors (NtRTIs) non-nucleoside reverse transcriptase inhibitors (NNRTIs) protease inhibitors (PIs) entry or fusion inhibitors integrase inhibitors (INSTIs)
__________ inhibit the viral reverse transcriptase, either by competing with natural nucleosides (NRTIs) or by reducing its catalytic activity (NNRTIs
Reverse transcriptase inhibitors
Nucleoside reverse transcriptase inhibitors (NRTIs):
Lack a 3’-OH for attachment of the next nucleotide
_______ was originally developed as an anticancer agent and the first drug to be approved for use in the treatment of AIDS
Zidovudine (aka azidothymidine, AZT)
______ target a hydrophobic allosteric site on reverse transcriptase
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
______ relies on a viral protease to properly cleave viral proteins in preparation for creating new viral particles
HIV
C-C motif chemokine receptor (CCR5) are G-protein–coupled receptor recognized by HIV and CCR5 antagonists inhibit HIV recognition of a prospective host cell
Entry or fusion inhibitors
Selzentry)
What are the 4 kinds of Integrase inhibitors (INSTIs)
HIV integrase
Raltegravir (Isentress) was the first integrase inhibitor (2007)
Elvitegravir was the second integrase inhibitor (2012)
Dolutegravir (2013)
____ is a enzyme responsible for integrating viral DNA into the host genome
HIV integrase
______ is active against Human Endogenous Retroviruses (HERVs) and possibly Epstein-Barr Virus, which have been suggested in the pathogenesis of relapsing-remitting MS
Raltegravir (Isentress)
what are the drugs for Pre-exposure prophylaxis (PrEP) against HIV infection
Tenofovir disoproxil/emtricitabine (trade name Truvada)
a fixed-dose combination of two antiretroviral drugs used for the treatment of HIV/AIDS developed by Gilead Sciences
300 mg of tenofovir disoproxil (NtRTI)
200 mg of emtricitabine (NRTI)
______ is a retrovirus containing RNA as its genetic material, and is responsible for AIDS.
HIV
The two main viral targets for anti-HIV drugs are the enzymes ____ and ____.
reverse transcriptase and protease
_____ is a group of viruses responsible for a number of diseases and range from the seasonal flu to recent global diseases such as swine flu (H1N1 virus) and bird flu (H5N1 virus)
Influenza virus
______ is the only oral influenza antiviral approved for use in Canada
______ is an inhaled medication
both are viral neuraminidase inhibitors
oseltamivir (Tamiflu)
zanamavir (Relenza)
both are viral neuraminidase inhibitors
neuraminidase is involved in the budding of new viruses from infected cells
How do neraminidase inhibitors work?
which prevent virions from being released from the surface of infected cells.
The flu virus contains (−)ssRNA and has two glycoproteins called ____ and ______ in its outer membrane.
haemagglutinin (HA) and neuraminidase (NA)
______ binds to the sialic acid moiety of glycoconjugates on the outer surface of host cells leading to adsorption and cell uptake.
_____ catalyses the cleavage of sialic acid from glycoconjugates. It aids the movement of the virus through mucus and releases the virus from infected cells after budding.
HA, NA
True or False: There are four important binding pockets in the active site. The sialic acid moiety is distorted from its normal chair conformation when it is bound.
True
The mechanism of the enzyme-catalysed reaction is proposed to go through an _______. Inhibitors were designed to mimic this state by introducing an endocyclic double bond.
endocyclic sialosyl cation transition state
_____ is where attachment takes place between the virus and the host cell
on the canyon floor there is a pore which opens into a hydrophobic pocket within the VP1 protein
pocket is either empty or occupied by a small molecule called a pocket factor
Canyon
Phase III clinical trials for ______ demonstrated that it had an effect on the common cold
Pleconaril
____ and ____ are inhibitors of HCV NS5A protein
Sofosbuvir and dasabuvir.
______ is is a carbocyclic nucleoside and is a agent acting against cytidine triphosphate synthetase
cyclopentenyl cytosine
______ is a A is an analogue of cyclopentenyl cytosine and is a agent acting against S-adenosylhomocysteine hydrolase
3-Deazaneplanocin A
_____ is a synthetic nucleoside that induces mutations in viral genes
dominant mechanism of action appears to be depletion of intracellular pools of GTP by inhibiting inosine-5′-monophosphate dehydrogenase
can also inhibit viral RNA-dependent RNA polymerase
used in combination to treat hepatitis C infection
Ribavirin
______ is thet first effective antiviral drug to reach the clinic
inhibits viral protein synthesis
used to treat smallpox in the 1960s
worries about terrorism has led to new research for novel antiviral agents effective against smallpox
Methisazone
______ are chemicals produced in the body which shut down infected host cells and limit the spread of virus.
Interferons
True or False: The best broad-spectrum antiviral agents appear to work on a variety of targets, reducing the chances of resistance.
True
