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What is the primary structure that encloses viral nucleic acid?
Naked viruses are less virulent than enveloped viruses.
False
What is the term used for a free-living virus particle?
virion
Viruses have a size range of _____ nm.
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Which of the following statements is true regarding virus structure?
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RNA viruses require the host's nucleus for their replication.
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Match the following viral components with their descriptions:
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Name one feature of the viral envelope that assists in its function.
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Which of the following drugs is an integrase inhibitor?
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Dolutegravir is known for having more side effects compared to other integrase inhibitors.
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What are the components of the new three-in-one regimen known as TLD?
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___ is a side effect associated with the use of integrase inhibitors.
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Match the following medications with their respective effects on dolutegravir levels:
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What is a significant limitation of antiviral therapy?
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Antivirals can effectively treat latent viruses.
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Name one main reason why viruses are difficult to treat.
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Acyclovir is an example of a __________ inhibitor.
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Match the following classes of antiviral drugs with their examples:
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What does the term 'virustatic' imply?
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Initial phases of viral infection are often symptomatic.
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What is the role of viral thymidine kinase in acyclovir's mechanism of action?
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Most antivirals are effective only when the virus is __________.
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Which of the following is NOT a class of antiviral drugs?
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Which of the following is a major side effect of interferons?
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Zanamavir is available as a tablet for treatment.
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What does HIV stand for?
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Immunoglobulins work against the virus ______, preventing attachment to host cells.
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Match the following immunoglobulins with their corresponding diseases:
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What is the mechanism of action of interferons?
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HIV can be transmitted through casual contact like hugging.
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List one mode of HIV transmission.
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The end-stage of infection with HIV is known as ______.
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Which of the following is NOT a type of interferon?
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Which side effect is associated with both Lamivudine and Stavudine?
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Tenofovir is effective in treating viruses resistant to NRTIs.
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What is a common side effect of Efavirenz?
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Zidovudine is particularly beneficial in preventing _____ infection.
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Match the following NRTIs with their respective key side effects:
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Which drug must be avoided with Rifampicin?
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Enfuvirtide needs to be administered orally to be effective.
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What does Maraviroc specifically block to prevent HIV entry into cells?
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Common side effects of Protease Inhibitors include _____ and _____ dysfunction.
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Which NNRTI is known for its potential teratogenic effects and should be taken on an empty stomach?
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Study Notes
Characteristics of a Virus
- Viruses are non-cellular organisms that rely on host systems for reproduction and metabolism.
- They are very small, ranging in size from 20 to 1400 nanometers.
- A free-living virus particle is referred to as a virion.
- The structure of a virion consists of viral nucleic acid (RNA or DNA) encased in a protein coat called a capsid.
- Some viruses have an envelope surrounding the capsid. This envelope has spikes that aid in attachment to host cells.
- Viruses without an envelope are known as naked viruses, which are often more virulent.
Viral Replication
- DNA viruses enter the host cell nucleus and directly generate new viruses.
Antiviral therapy
- Antivirals are virustatic, meaning they suppress viral replication rather than killing the virus. They rely on the host's immune system to eliminate the virus.
- Antivirals rarely affect latent viruses.
- Antiviral treatment is challenging for the following reasons:
- They do not exhibit selective toxicity due to viral integration into host DNA.
- Many antivirals are only effective while the virus is actively replicating.
- Early stages of viral infection are often asymptomatic, resulting in treatment delays.
- Rapid mutations allow viruses to evade detection and develop drug resistance.
Classes of Antiviral Drugs
- Antiviral drugs are classified based on their mechanism of action, including:
- Nucleoside/nucleotide reverse transcriptase inhibitors
- Non-nucleoside reverse transcriptase inhibitors
- Protease inhibitors
- Neuraminidase inhibitors
- Fusion/entry inhibitors
- Integrase inhibitors
- Biologics and immunomodulators
Sites of Action of Antiviral Drugs
- Antiviral drugs work by targeting different stages of the viral life cycle, including viral entry, replication, assembly, and release.
DNA Polymerase Inhibitors
- Acyclovir, a guanosine analogue, is an example of a DNA polymerase inhibitor.
- Acyclovir is activated by viral thymidine kinase, converting it to acyclo-guanosine monophosphate (GMP).
- GMP is further converted to acyclovir di- and triphosphate (GTP) by host cell kinases.
- These forms of acyclovir inhibit viral DNA polymerase, preventing viral replication.
- Increased resistance to these drugs is observed due to annual variations in influenza strains.
Biologics: Immunoglobulins
- Immunoglobulins are produced by activated B cells and can also be obtained through biotechnology.
- They target the viral envelope, preventing attachment to host cells.
- Biologics bind to foreign substances, triggering macrophage and natural killer (NK) cell destruction.
- Specific immunoglobulins provide immediate protection against viral infections such as hepatitis, rabies, tetanus, and varicella zoster.
Immunomodulators: Interferons
- Interferons are inducible proteins produced by the body and can be synthesized using recombinant DNA technology.
- Interferons inhibit the translation of viral mRNA into viral proteins.
- They are administered intravenously and have a short duration of action, requiring frequent dosing.
- Pegylated versions of interferons are available, which have a longer duration of action.
- The three main types of interferons are interferon-α, interferon-β, and interferon-γ.
- Common side effects include alopecia, fever, dizziness, and headache.
- Interferons are contraindicated in patients with hepatic dysfunction.
HIV
- HIV, the human immunodeficiency virus, is a retrovirus with its genetic material stored in RNA. Complementary DNA (cDNA) is generated from this RNA.
- AIDS, acquired immune deficiency syndrome, is the end-stage of HIV infection.
- AIDS is characterized by an impaired immune system, leading to susceptibility to opportunistic infections.
HIV Transmission
- HIV spreads through contact with infected bodily fluids, including:
- Blood
- Semen and vaginal fluids
- Mother-to-child transmission
- Accidental needle stick injury
- Sharing needles
- Artificial insemination with infected sperm
- Organ transplantation using infected organs
- HIV is not transmitted through casual contact, touching objects handled by an infected individual, or kissing*.
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
- NRTIs are a class of antiviral drugs used to treat HIV infection.
- NRTIs interfere with the activity of HIV reverse transcriptase, an enzyme required for HIV reproduction.
- Common NRTIs include:
- Zidovudine (AZT)
- Lamivudine (3TC)
- Stavudine (d4T) - phased out due to side effects
- Tenofovir (TDF)
- NRTIs are frequently combined to improve effectiveness and reduce the emergence of drug resistance.
NRTI Dual Combinations
- Recommended NRTI combinations:
- Tenofovir + lamivudine
- Zidovudine + lamivudine
- Abacavir + lamivudine
- Tenofovir + emtricitabine
- Hazardous NRTI combinations:
- Stavudine + didanosine*
- Tenofovir + didanosine
- Antagonistic NRTI combinations:
- Stavudine + zidovudine
NRTI Class Side Effects
- NRTIs can lead to various drug-resistant mutations.
- Common side effects include:
- Impaired mitochondrial function, resulting in hepatic steatosis and hyperlactatemia (lactic acidosis)
- Lipodystrophy (fat redistribution)
- Cardiomyopathy
- Myopathy, neuropathy, and pancreatitis
- Myelosuppression (neutropenia and severe anemia)
- NRTIs vary in their potential for inducing these side effects, with stavudine having the highest risk, followed by didanosine, zidovudine, and then lamivudine, abacavir, and tenofovir.
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
- NNRTIs are another class of antiretroviral drugs used to treat HIV infection.
- Commonly used NNRTIs include:
- Efavirenz (EFV)
- Nevirapine (NVP)
- Rilpivirine (RPV)
- Etravirine (ETV)
- NNRTIs bind to HIV reverse transcriptase, altering its structure and reducing its efficiency.
- They are primarily active against HIV-1.
NNRTIs: Individual Drugs
- Nevirapine (NVP):
- Induces CYP3A4, reducing the activity of co-administered antiretrovirals.
- Is lipophilic, meaning it can cross the placenta and enter breast milk.
- Efavirenz (EFV):
- Preferred NNRTI for treatment.
- A potent inducer of CYP450 enzymes.
- Has a higher bioavailability when taken with a fatty meal, increasing potential toxicity.
- Evidence suggests teratogenicity.
- Common side effects include insomnia, dizziness, depression, nightmares, memory loss, psychosis, and impaired concentration.
- Rilpivirine (RPV) and Etravirine (ETV):
- Usually reserved for third-line treatment.
- RPV can only be used if the viral load is less than 100,000 copies/mL.
- RPV cannot be used with rifampicin.
- Cross-resistance is common within the class of NNRTIs.
Protease Inhibitors (PIs)
- PIs are antiretroviral drugs that target HIV protease, an enzyme required for viral assembly.
- PIs prevent the cleavage of viral proteins into essential enzymes and structural proteins, inhibiting viral maturation and release.
- Common PIs include:
- Lopinavir/ Ritonavir (FDC)
- Atazanavir
- Indinavir
- Saquinavir
- Nelfinavir
- Common side effects include paresthesia, hyperglycemia, hypercholesterolemia, lipodystrophy, fatigue, sleep disturbances, rhabdomyolysis, and liver dysfunction.
Protease Inhibitors: Specific Drugs
- Lopinavir/ Ritonavir (FDC):
- First-line protease inhibitors.
- Dosage needs to be doubled or ritonavir added when co-administered with rifampicin.
- Saquinavir is also compatible with rifampicin, but avoid rifampicin with other PIs.
- Disadvantages:
- Poorly tolerated
- Cross-tolerance is common
- Frequent drug interactions
- PIs have poor oral bioavailability and are best taken with high-fat meals.
- PIs are metabolized in the liver by CYP450 enzymes.
- Never give saquinavir without boosting it with low dose of ritonavir.
Fusion Inhibitors - Enfuvirtide
- Enfuvirtide targets viral transmembrane glycoprotein gp41, preventing conformational changes necessary for HIV entry into host cells.
- It is used as part of rescue regimens for multi-drug resistant HIV or intolerance to other antiretrovirals.
- Given subcutaneously twice daily in the upper arm, abdomen, or anterior thigh.
- Common side effects include flu-like symptoms, headache, dizziness, mood changes, gastrointestinal effects, and hypersensitivity..
Fusion Inhibitors - Maraviroc (MVC)
- Maraviroc targets CCR5, a host cell receptor hijacked by some HIV strains to gain entry into the cell.
- HIV can exhibit preference for either CCR5 or CXCR4 (dual tropic) or exhibit affinity for one receptor.
- Maraviroc blocks CCR5 receptors, preventing viral entry into the cell; it only works against strains that use CCR5.
- A test must be performed to determine the HIV strain's tropism before using MVC.
- Reduce MVC dose when co-administered with protease inhibitors.
Integrase Inhibitors (INSTI)
- INSTIs block the activity of integrase, a viral enzyme that inserts the viral genome into the host cell's DNA.
- Commonly used INSTIs include:
- Raltegravir
- Dolutegravir
- Elvitagravir
- Dolutegravir has fewer side effects and fewer negative interactions with other medications.
- South Africa is rolling out a new regimen known as TLD (three-in-one, fixed-dose combination) that includes dolutegravir, lamivudine, and tenofovir.
- Dolutegravir interactions:
- Rifampicin lowers dolutegravir levels.
- Dolutegravir increases metformin levels.
- Carbamazepine, phenobarbital, phenytoin (anticonvulsants), antacids, sucralfate, multivitamin and nutritional supplements decrease dolutegravir levels.
- Side effects include insomnia, fatigue, abnormal dreams, anemia, renal impairment, and lipoatrophy (loss of fat tissue).
Drug Regimens
- First-line treatment in South Africa includes two NRTIs and dolutegravir (e.g., TLD).
- Protease inhibitors are not used as first-line therapies due to long-term toxicity.
- To prevent mother-to-child transmission:
- Newly diagnosed pregnant women should initiate FDC regimen immediately.
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Description
This quiz covers the essential characteristics of viruses, including their structure and classification into enveloped and naked viruses. It also explores the viral replication process and the role of antiviral therapies in managing viral infections. Test your knowledge on how viruses interact with host systems and how treatments are designed to combat them.
