Lecture 25: Antivirals Flashcards
What are Viruses?
Obligate intracellular parasites
What does it mean to be an obligate intracellular parasite?
They rely on host biosynthetic machinery to reproduced
What do viruses exist as when not inside an infected cell?
They exist as independent particles called virions
What do viruses exist as when not inside an infected cell?
They exist as independent particles called virions
What do Virions consist of?
- Double or single stranded DNA or RNA
- A protein coat (capsid)
- Some possess a lipid envelope
What is the Capsid?
The protein coat of a Virion
What is the lipid envelope of a virion derived from?
The host cell
What can the genetic material of a Virion be?
Double or single stranded DNA or RNA
What can the lipid envelope or protein coat of a virion contain?
Antigenic glycoproteins that can infect the host
What is the viral range?
The group of cell types (or species) that a virus can infect
What is the size comparison between a virus and a bacterium?
Viruses are 1/100th of the average bacterium
What is a Bacteriophage?
Viruses that only infect bacteria
What do most animal viruses not cross?
Phyla, and some only infect closely related species
What are the three virus shapes?
Helical, Icosahedral, Complex
What is pathogenicity?
The ability of viruses to cause disease
What is Virulence?
The degree of pathogenicity
What is latency?
When some viruses can remain dormant in organisms
What are carriers?
People chronically infected and that serve as reservoirs of infectious viruses
Do all viruses cause disease?
No, there a GI viruses and skin viruses that are part of the microbiome
What does it mean to be low virulence?
Does not cause significant disease in humans
What does the virulence of a virus change depending on?
The type of the virus and from person to person
What is the difference between pathogenicity and virulence?
Pathogenicity is just does it cause disease or not? And if it does cause disease virulence is the intensity of the disease
What are the four steps in the life cycle of viral replication?
- Absorption
- Penetration
- Replication
- Release
What do the surfaces of viruses have?
Proteins that bind to receptor protein on the host cell
What determines the host range of a virus?
The surface proteins of a virus that bind to a receptor protein on a host cell
What begins the infection process of a virus?
The surface proteins of a virus binding to the receptor protein on a host cell
What happens once binding proteins on viruses bind to receptors on the host cell?
Viral DNA or RNA crosses the cytoplasm or nucleus
What happens once a virus enters the cell?
Viral DNA or RNA interacts with host machinery for translating DNA or RNA into viral protein
What happens once newly synthesized viral protein is created in the host cell?
Newly synthesized virion particles are released to continue infection cycle
What are the two types of viruses?
RNA and DNA viruses and can be single-stranded or double double-stranded
What do most DNA viruses do?
Enter the host cell nucleus where the viral DNA is integrated into the host genome and transcribed into mRNA
What transcribed DNA viruses into mRNA?
Host DNA-dependant RNA polymerase
What is an exception to DNA viruses and why?
Poxviruses carry their own DNA-dependant RNA polymerase
What does viral genome replication of viruses require?
DNA dependant DNA polymerase from the host or virus
Where can pox viruses replicate and why?
They replicate in the host cell cytoplasm because they have their own DNA-dependant RNA polymerase
What do double stranded RNA viruses require?
RNA-dependent RNA polymerases
What does the RNA-dependant RNA polymerase do with RNA viruses?
Acts a transcriptase to transcribe mRNA and a replicase to replicate the viral genome
Where do most RNA viruses complete their replication?
In the host cell cytoplasm, but some (influenza) are transcribed in the nucleus
Where do RNA viruses get RNA-dependant RNA polymerases?
They bring their own
What does a transcriptase to?
Transcribes mRNA
What does a replicase do?
Replicates the viral genome
What is the main characteristic of Retroviruses?
They have an RNA genome that directs the formation of a DNA molecule
What machinery is used with retroviruses?
The enzyme reverse transcriptase
What does reverse transcriptase do?
It copies viral RNA into DNA (RNA dependant DNA polymerase)
What is done with the resulting DNA in retroviruses?
It is integrated into the host DNA (then transcribed into mRNA and translated into protein by host enzymes)
Do retroviruses kill their host cells?
Most don’t immediately kill their host cells, but rather infected host cells can continue to replicate producing daughter cells with integrated proviral DNA
Where does the reverse transcriptase for retroviruses come from?
The virus and not the host
What do vaccines consist of?
Live-attenuated or killed viruses, or viral proteins or mRNA
When can antiviral drugs exert actions?
At several stages of viral replication including •viral entry •nucleic acid synthesis •protein synthesis •viral packaging •virion release
What can Combination therapy result in?
Greater clinical effectiveness against viral infections and can also prevent or delay the emergence of resistance
What does it mean for anti-viral drugs to be virustatic?
They are only active against replicating viruses and do not affect latent viruses
What is an example of an Anti-Herpes Drug?
Acyclovir
How does Acyclovir work?
It is a nucleoside analog and lacks the hydroxyl group important for forming the backbone and blocks the lifecycle of the virus because newly synthesized DNA is inactive
Why doesn’t Acyclovir affect the human genome?
Because it must be phosphorylated to acyclovir-triphosphate to be incorporated into viral DNA and can only be added by herpes-simplex virus thymidine kinase
What can Acyclovir resistance in herpes be caused by?
- Impaired production of thymidine kinase
- Altered thymidine kinase substrate specificity
- Altered viral DNA polymerase
What is HIV?
A lentivirus that lead to chronic persistent infection with gradual onset of clinical symptoms
Which cells does HIV infect?
CD4+ T cells
What happens when CD4+ T cells decline below a critical level?
Cell mediated immunity is lost and the body become susceptible to opportunistic infections
What kind of virus is HIV?
A retrovirus
What do people with HIV die from?
They don’t die from HIV, they die from infections that they cant fight off because they have no more CD4+ cells
What does current HIV treatment usually involve?
3 or more antiretroviral drugs
What is HAART?
Highly active antiretroviral therapy involving drug combinations that can slow or reverse the increases in viral RNA load that normally accompany progression of disease
What does HIV infection begin with?
Attachment of HIV envelope proteins called gp120 to CD4 and CCR5 receptors on T-cells
How do HIV entry inhibitors work?
They interfere with binding, fusion and entry of an HIV virion into a human cells
What is an example of an entry inhibitor for HIV?
Maraviroc
How does Maraviroc work?
It is a CCR5 receptor antagonist so it interferes with HIV binding to T cell
How does HIV reverse transcriptase enzyme synthesize DNA?
From HIV RNA using nucleosides in the host T-cell (RNA dependant DNA polymerases)
What are NRTI?
Small molecule drugs that are similar to the host nucleosides and are incorporated into new HIV DNA chain but they lack the 3’ hydroxyl group from attachment of the next nucleoside
What is integrase?
A viral enzyme that inserts viral genome into the DNA of the host cell
What do Integrase inhibitors do?
Block the action of integrase to inhibit HIV proliferation
What is an example of an Integrase inhibitor?
Raltegravir
How does Raltegravir work?
Blocks the action of integrase to inhibit HIV proliferation
What is dependant on aspartate proteases?
Assembly of infection HIV virions
What do Aspartate Proteases do?
Cleaves precursor proteins to form the final structural proteins of the mature virion core
What are HIV protease inhibitors based on?
Molecular characterization of the active site of the viral enzyme
What are protease inhibitors used in combination with?
Reverse transcriptase inhibitors
What does the M2 protein do in terms of influenza?
Functions as a proton ion channel required at the onset of infection to permit acidification of the virus core which activates viral RNA transcriptase
What is Amantadine used to treat?
Influenza
What does Amantadine do?
Blocks proton transfer through M2, thus blocking acidification and the initiation of viral transcription
What Amantadine prophylactic against?
Influenza A and not B and can reduce the duration of symptoms if given within 48 hours after contact
What does Zanamivir treat?
Influenza
What is Zanamivir an inhibitor of?
Neuraminidases produced by influenza A and B
What do Neuraminidases do?
Cleave sialic acid residues from viral proteins that enable virus to be released from the host cell
