Antivirals and Diagnostic Virology Flashcards
List the 3 classes of drugs for Influenza antivirals
- Uncoating
- Neuraminidase
- Cap-dependent Endonuclease inhibitor
Describe uncoating
Rimantadine/Amantadine blocks uncoating, can only be used on Influenza A, and all current strains are resistant
Describe Neuraminidase inhibitors
Blocks the release of the virus by blocking the viral neuraminidase. The most common is Tamiflu
Describe cap-dependent Endonuclease inhibitor
Xofluza prevents the virus from taking cellular mRNA caps and using them to make viral mRNA. As a result, viral RNA cant’t be transcribed into mRNA, and viral proteins are not made
Describe the antiviral Ribavirin
- Not specific for one virus and can be used on respiratory syncytial virus, hepatitis C virus, and hemorrhagic fever viruses
- Ribavirin works by lowering guanine nucleotides in the cell, making replication harder
- Ribavirin is a teratogen. Two forms of birth control should be used while taking ribavirin and continued for six months after use
What steps in HIV replication are inhibited by antivirals?
1) Entry inhibitors block receptor/co-receptor binding or membrane fusion and entry
2) Reverse transcriptase inhibitors, 2 classes:
-Nucleoside Reverse Transcriptase Inhibitors (NRTI)-chain terminators prevent the chain from being elongated
-Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI)-bing to reverse transcriptase and prevents its ability to make DNA
-Both block the ability of the virus to make a DNA copy of itself
3) Integrase Inhibitors prevent the virus from inserting the viral DNA into the cellular DNA
4) Protease Inhibitors block the maturation of the viral particle
What are the 3 classes of HCV drugs?
1) Viral protease inhibitors block the cleavage of the polyprotein and stop replication after this step. The virus cannot replicate its genetic material
2) Viral RNA-dependent RNA polymerase inhibitors block the ability of the virus to replicate its RNA
3) NS5A inhibitors block RNA production and assembly
In regards to Herpesviruses, Acyclovir compounds block the viral polymerase and interfere with viral DNA production. What do they all need to by activated by?
A viral thymidine kinase
This means that the acyclovirs will be preferentially activated in an infected cell that has the viral thymidine kinase
When referring to Herpesviruses, what is Acyclovir/Valacyclovir?
Valacyclovir is a prodrug of acyclovir. It is converted to acyclovir in the
body and requires less dosing than acyclovir. Both treat HSV and VZV herpesviruses.
When referring to Herpesviruses, what is Famciclovir and Penciclovir?
Famciclovir is oral, and Penciclovir is topical. They are the same active compound and can also treat HSV and VZV herpesviruses.
When referring to Herpesviruses, what is Valganciclovir and Ganciclovir?
Valganciclovir and Ganciclovir have more side effects and are used to treat the herpesvirus CMV
Why is viral diagnostics used?
- It is usually used to confirm a diagnosis
- Diagnosing a virus is necessary for prescribing the correct antiviral drugs
- It can help monitor chronic infections. Is the virus level increasing or decreasing in the body? Is the antiviral tx working?
- Monitor the prevalence of a virus in the community, i.e. epidemiological monitoring
In cytology, viral infections are determined by looking for….
viral inclusion bodies, syncytia, or using detector antibodies for viral proteins
Vaccines require large quantities of virus. Any many vaccines are produced in _________
cultured cells
Cell culture can be used to diagnose an infection, but __________ are rapidly replacing the need for viral culture
nucleic acid tests
What are ELISA or EIA used for?
1) To detect antibodies present in the body against a specific virus
2) *IgM, which would indicate an acute infection
3) *IgG, which could specify an acute, chronic, or past infection
4) Test for the presence of a viral antigen, which indicates active infection
5) *The test is specific for one virus
6) Check for vaccine efficacy
7) All tests can have false positives or false negatives
Describe Lateral Flow Assay
1) It is essentially a quick, easy test and is like an ELISA or EIA
2) Can detect presence of viral antigens or antibodies
3) Quick and can be done in minutes
4) Can be done at doctor’s or at home
5) Have to know what virus to test (one virus tested per assay)
6) Test might not pick up the new strain if the virus undergoes antigen drift
Describe Nucleic Acid Amplification Tests (NAAT)
1) Very sensitive and can amplify small amounts of starting material
2) Usually pick up an infection if it is present
3) A specialized NAAT can be used to determine the amount of virus in a person. This is often done in chronic infections to see if antiviral tx is working
4) Test done at doctors (in-house) but sent to a lab - means results take several days
5) NAAT tends to be more expensive than lateral flow assays
6) There are nucleic acid amplification tests that can test for several infections at once. These are costly and usually not done unless the person is hospitalized
T/F: Most tests are not 100% accurate
True - there can be false positives and false negatives
The ________ of the test is how many people with the disease will test positive
sensitivity
If 100 people have been infected with the flu and only 70 of them test positive on the test, then the sensitivity of the test is 70%
The _______ of the test is how many people who DO NOT have the disease will test negative
specificity
If 100 people who are not infected with the flu take the test and 5 of them test positive, then the specificity is 95.5%. Remember, you are looking for a number telling you the percentage of people who do not have the disease who test negative
When the prevalence of infection is low, testing can have ______
limited utility
What are the different classes of inhibitors for HIV?
-Entry inhibitors
-Reverse Transcriptase (NRTI, NNRTI)
-Integrase Inhibitor
-Protease Inhibitors
What are the different classes of inhibitors for HCV?
-Protease inhibitors
-RNA Polymerase Inhibitors
-NS5A Inhibitors
What is the function of entry inibitors
block receptor/co-receptor binding or membrane fusion and entry
What is the function of reverse transcriptase (NRTI and NNRTI)
-(NRTI)-chain terminators prevent the chain from being elongated
-Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI)-bing to reverse transcriptase and prevents its ability to make DNA
-Both block the ability of the virus to make a DNA copy of itself
What is the function of Integrase inhibitors
prevent the virus from inserting the viral DNA into the cellular DNA
What is the function of protease inhibitors
block the cleavage of the polyprotein and stop replication after this step. The virus cannot replicate its genetic material (block the maturation of the viral particle)
What is the function of RNA polymerase inhibitors
Viral RNA-dependent RNA polymerase inhibitors block the ability of the virus to replicate its RNA
What is the function of NS5A inhibitors
block RNA production and assembly