Podcast
Questions and Answers
What does the therapeutic index (TI) represent in the context of antiviral drugs?
What does the therapeutic index (TI) represent in the context of antiviral drugs?
Which method involves using known active compounds through chemical modification?
Which method involves using known active compounds through chemical modification?
What is the potential benefit of using AI tools in drug development?
What is the potential benefit of using AI tools in drug development?
What role do mutations conferring drug resistance play in antiviral research?
What role do mutations conferring drug resistance play in antiviral research?
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How do capsid-binding drugs function in antiviral therapy?
How do capsid-binding drugs function in antiviral therapy?
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What was a significant issue with early vaccination technology?
What was a significant issue with early vaccination technology?
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What technological advancement accelerated vaccine development in the mid-20th century?
What technological advancement accelerated vaccine development in the mid-20th century?
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Which of the following describes a panzootic?
Which of the following describes a panzootic?
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What was the mortality rate of potential avian influenza infections in humans identified during the H5N1 outbreak?
What was the mortality rate of potential avian influenza infections in humans identified during the H5N1 outbreak?
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Why do ethical concerns arise in the context of vaccines?
Why do ethical concerns arise in the context of vaccines?
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What challenge did vaccine production face during the H5N1 avian influenza outbreak?
What challenge did vaccine production face during the H5N1 avian influenza outbreak?
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Which of the following statements is true regarding the immune response to vaccines?
Which of the following statements is true regarding the immune response to vaccines?
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What aspect of vaccine safety needs careful consideration?
What aspect of vaccine safety needs careful consideration?
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What role do adjuvants play in vaccination?
What role do adjuvants play in vaccination?
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Which type of vaccine typically does not require adjuvants?
Which type of vaccine typically does not require adjuvants?
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What is a major concern regarding the safety of vaccines?
What is a major concern regarding the safety of vaccines?
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What is the effect of vaccines on viral load and transmission?
What is the effect of vaccines on viral load and transmission?
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What problem exists in the development of antiviral vaccines?
What problem exists in the development of antiviral vaccines?
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Which of the following can enhance cellular immunity without involving antibodies?
Which of the following can enhance cellular immunity without involving antibodies?
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What is a potential consequence of vaccines on virus mutation?
What is a potential consequence of vaccines on virus mutation?
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What are researchers developing to improve vaccination delivery?
What are researchers developing to improve vaccination delivery?
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What characteristic is shared by live wild-type viruses used in antiviral vaccines?
What characteristic is shared by live wild-type viruses used in antiviral vaccines?
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Why are live attenuated viruses considered generally the most effective type of antiviral vaccine?
Why are live attenuated viruses considered generally the most effective type of antiviral vaccine?
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What is a disadvantage of inactivated whole virus vaccines?
What is a disadvantage of inactivated whole virus vaccines?
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Which statement best describes subunit vaccines?
Which statement best describes subunit vaccines?
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What is a key feature of chimeric vaccines?
What is a key feature of chimeric vaccines?
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What is a critical challenge regarding live attenuated viruses?
What is a critical challenge regarding live attenuated viruses?
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What is a disadvantage of subunit vaccines?
What is a disadvantage of subunit vaccines?
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What is a benefit of using inactivated whole virus vaccines?
What is a benefit of using inactivated whole virus vaccines?
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What is a significant advantage of RNA and DNA vaccines?
What is a significant advantage of RNA and DNA vaccines?
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Which is a common misconception about the risks associated with live attenuated viruses?
Which is a common misconception about the risks associated with live attenuated viruses?
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What is the primary mechanism by which acyclovir triphosphate inhibits viral DNA synthesis?
What is the primary mechanism by which acyclovir triphosphate inhibits viral DNA synthesis?
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Which drug has a higher toxicity due to phosphorylation by cellular kinases instead of viral kinases?
Which drug has a higher toxicity due to phosphorylation by cellular kinases instead of viral kinases?
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What is the role of Nevirapine (NVP) in HIV treatment?
What is the role of Nevirapine (NVP) in HIV treatment?
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Why are nucleoside analogues like acyclovir required to be activated by phosphorylation?
Why are nucleoside analogues like acyclovir required to be activated by phosphorylation?
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What is the function of integrase inhibitors like Raltegravir?
What is the function of integrase inhibitors like Raltegravir?
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What unique aspect of Ritonavir contributes to its role as a protease inhibitor for HIV-1?
What unique aspect of Ritonavir contributes to its role as a protease inhibitor for HIV-1?
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Which of the following statements about the activation of acyclovir is true?
Which of the following statements about the activation of acyclovir is true?
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How does AZT lead to chain termination in viral DNA synthesis?
How does AZT lead to chain termination in viral DNA synthesis?
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Which type of drug was used in the prevention of mother-to-child transmission (PMTCT) of HIV?
Which type of drug was used in the prevention of mother-to-child transmission (PMTCT) of HIV?
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What impact can mutations in the reverse transcriptase enzyme have on the treatment with Nevirapine?
What impact can mutations in the reverse transcriptase enzyme have on the treatment with Nevirapine?
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What is the primary function of neuraminidase (NA) inhibitors in relation to the influenza virus?
What is the primary function of neuraminidase (NA) inhibitors in relation to the influenza virus?
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Which antiviral drugs are mentioned as effective for treating severe diseases caused by influenza virus?
Which antiviral drugs are mentioned as effective for treating severe diseases caused by influenza virus?
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Why is combination therapy generally needed in the treatment of HIV?
Why is combination therapy generally needed in the treatment of HIV?
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What is the status of several drugs targeting SARS-CoV2?
What is the status of several drugs targeting SARS-CoV2?
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Which of the following is a recent trend in antiviral drug research?
Which of the following is a recent trend in antiviral drug research?
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What is the significance of Highly Active Antiretroviral Therapy (HAART) in HIV treatment?
What is the significance of Highly Active Antiretroviral Therapy (HAART) in HIV treatment?
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Zanamivir and Oseltamivir are stockpiled for which reason?
Zanamivir and Oseltamivir are stockpiled for which reason?
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Which of the following describes the future of antiviral drug research?
Which of the following describes the future of antiviral drug research?
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Study Notes
Antiviral Vaccines
- Vaccination is the most effective means to prevent viral infections
- Serious adverse effects must be investigated, however they are very rare.
- If a vaccine is not 100% safe/effective, it raises ethical concerns
- Vaccination has significantly decreased diseases like smallpox, polio, measles, mumps, rubella, and congenital rubella syndrome.
Antiviral Vaccines - History
- Early vaccine technology was crude but effective
- Chinese doctors used powdered smallpox scabs for early immunization
- Lady Montagu introduced variolation to England
- Jenner's work with cowpox was a milestone in smallpox prevention
- Pasteur and collaborators developed an early rabies vaccine
- Milestones in antiviral vaccine development include early use of smallpox scabs, variolation, cowpox, and later, developments in viral culture technologies, including cell culture and embryonated eggs, which revolutionized vaccine development.
- The use of primary cell culture and immortalized cell lines accelerated vaccine development during the 1950s and 1960s. This led to the development of vaccines for diseases like polio, measles, mumps, and rubella
- Crude vaccines from natural products worked well, but due to limitations, serious side effects occurred. Fear of epidemics often motivated vaccination.
Antiviral Vaccines - Classical Categories
- Current antiviral vaccines fall into categories like live wild-type, live attenuated, inactivated, subunit, and viral-like particles (VLPs)
- Live attenuated viruses are generally very effective due to serial passage and in vitro cultivation of viruses reducing their pathogenicity.
- Live wild-type viruses replicate poorly in unexpected hosts, but share immunogenic determinants with related viruses such as vaccinia virus
- Inactivated viruses are treated with chemicals like formaldehyde or organic solvents to inactivate them.
- Subunit vaccines consist of purified viral proteins, offering simplicity and stability. These vaccines typically have less efficacy than live vaccines, so boosters are often required.
- Viral-like particles (VLPs) are often more effective than single purified proteins.
Antiviral Vaccines - Newer Categories
- Chimeric vaccines are live, genetically modified organisms that express targeted viral proteins. These can deliver antigens to specific locations in the body.
- RNA and DNA vaccines introduce mRNA or DNA plasmids encoding viral proteins for transient expression in host cells.
- Nanoparticle vaccines (including VLPs) use synthetic nanoparticles to display viral antigens and can be combined with adjuvants.
Antiviral Vaccines - Safety
- Current vaccines are the safest ever marketed but not 100% safe.
- The history of vaccine developments has seen unfortunate incidents due to incomplete knowledge, but new surveillance methods enhance safety.
- Certain significant adverse events have been documented in the past.
Antiviral Vaccines - Herd Immunity
- Herd immunity results from high rates of vaccination in a population, effectively limiting the spread of a viral pathogen.
- Unvaccinated individuals are protected by reaching a threshold of "dead-end hosts".
- Community immunity levels can change due to vaccination rates and viral diversity.
Antiviral Vaccines - Ethical Issues
- Individuals refusing vaccination raise ethical questions about managing infected individuals and preventing further spread.
- Non-vaccinated individuals should not be excluded from essential services.
- Communities should prioritize protection of vulnerable members.
- Vaccination programs should consider the healthcare burdens associated with vaccine-preventable diseases and ensure equitable compensation for vaccine-related adverse events.
Antiviral Drugs
- The discovery and use of antiviral compounds is relatively recent, starting in the 1960s.
- Viral replication within human cells poses challenges to drug discovery.
- Broad-spectrum antivirals face limitations because of the large number of viruses, leading to less interest, as available vaccines also reduce the drive to develop new antiviral compounds.
- Discovering and obtaining antiviral drugs include methods like serendipity, modifying known compounds, high-throughput screening assays, and rational design strategies (including use of 3D structures of viral proteins)
Antiviral Drugs - Mechanism of Action
- Antivirals generally target specific steps of the virus life cycle such as attachment, entry, uncoating, viral gene expression, genome replication, assembly, maturation, and release.
Antiviral Drugs - Specific Targets
- Drugs are developed targeting viral enzymes for attachment, entry, uncoating, genome replication, etc
- Examples of viral targets in HIV are receptors, reverse transcriptase, protease, integrase
Antiviral Drugs - Therapeutic Index (TI)
- TI is the ratio of TD50 (toxic dose in 50% of population) to ED50 (effective dose in 50% of population).
- A higher TI is preferred as it signals less toxicity for a given therapeutic effect.
Antiviral Drugs - Attachment/Entry Inhibition
- Drugs can directly bind to virions or virus receptors / co-receptors, blocking fusion.
- Examples include Maraviroc blocking HIV-1 co-receptor CCR5 and Enfuvirtide binding to HIV to block conformational changes
Antiviral Drugs - Uncoating Inhibition
- Drugs can block ion channels in the virion envelope to prevent the interior acidification needed for viral release.
- Amantadine is an example of this type.
Antiviral Drugs - Nucleic Acid Synthesis Inhibitors
- Nucleoside analogues are incorporated into the growing viral genome, which prematurely terminates viral genome replication
- Acyclovir is an example that's phosphorylated by viral kinases
- AZT is a nucleoside analogue with an altered sugar moiety to cause termination in DNA synthesis.
- Non-nucleoside RT inhibitors (NNRTIs) like Nevirapine inhibit viral enzymes that are needed for genome replication.
Antiviral Drugs - Integrase Inhibitors
- Integrase inhibitors like Raltegravir block viral DNA insertion into the host chromosome.
- These are often part of combination therapies.
Antiviral Drugs - Protease Inhibitors
- Protease inhibitors interfere with virus assembly and maturation.
- Ritonavir is an example of a peptidomimetic protease inhibitor.
Antiviral Drugs - Neuraminidase Inhibitors
- Neuraminidase inhibitors block the release of influenza viruses from infected cells.
- Examples are Zanamivir (Relenza) and Oseltamivir (Tamiflu).
Antiviral Drugs - HIV Targets
- HAART (Highly Active Antiretroviral Therapy) often targets multiple steps in the replication cycle.
Antiviral Drugs - SARS-CoV-2 Targets
- Several drugs are under clinical trials for SARS-CoV-2 targeting multiple steps in virus replication.
Antiviral Drugs - Future
- Active research in understanding and targeting viruses is ongoing.
- New viral targets lead to new drug development.
- Successes against some viruses (HIV, influenza, herpes) provide hope for success against other viruses.
Final Exam
- The final exam covers lectures 5 through 12 and some content from earlier lectures.
- The format is similar to the midterm, including multiple-choice, fill-in-the-blank, and short answer questions, including application questions.
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Description
Explore the significant role of antiviral vaccines in preventing viral diseases and their historical development. This quiz covers the evolution of vaccination practices, from early methods like variolation to modern advancements in vaccine technology. Test your knowledge on key milestones and ethical concerns surrounding vaccine safety and effectiveness.
