MSOP1016: Science of Medicines - Antiviral Drugs against RNA Viruses Quiz
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Questions and Answers

What type of viruses do antiviral drugs against RNA viruses like HIV target?

RNA viruses

Who authored the article 'Approved antiviral drugs over the past 50 years'?

De Clercq E, Li G

In which book and chapter can you find information on Acyclic nucleoside analogues?

Foye's Principles of Medicinal Chemistry, Chapter: Viral chemotherapy, general approaches

What is the main focus of Lecture 14 on Nucleoside & Nucleotide analogues?

<p>Discussing strategies employed for development of newer generations of drugs</p> Signup and view all the answers

What are the three main classes of anti-viral therapeutic agents used to treat HIV?

<p>Nucleoside reverse transcriptase inhibitors, Non-nucleoside reverse transcriptase inhibitors, Protease inhibitors</p> Signup and view all the answers

What is the structure of HIV and how does it replicate within host cells?

<p>HIV is a retrovirus that inserts a DNA copy of its genome into host cells to replicate.</p> Signup and view all the answers

What are some limitations of current anti-viral therapeutic agents used to treat HIV?

<p>Rapid mutation rate of HIV, drug resistance, limited effectiveness in eradicating the virus</p> Signup and view all the answers

Describe the key challenges associated with developing therapeutics for HIV.

<p>Viral mutation rate, drug resistance, complexity of viral life cycle</p> Signup and view all the answers

What are Nucleoside reverse transcriptase inhibitors (NRTIs) and how do they work against HIV?

<p>NRTIs are drugs that inhibit the reverse transcriptase enzyme, preventing viral DNA synthesis.</p> Signup and view all the answers

Why is it important to understand the genetic variation and subtypes of HIV?

<p>Different subtypes may exhibit varying virulence and resistance to medications.</p> Signup and view all the answers

What are the two viral enzymes most commonly targeted by clinically useful drugs for HIV treatment?

<p>Reverse transcriptase and Protease</p> Signup and view all the answers

Which viral protein interacts with CD4 on host T-cells during the adsorption and penetration process of HIV?

<p>Gp120</p> Signup and view all the answers

What is the role of viral reverse transcriptase in the replication of the HIV genome?

<p>It converts viral RNA into DNA</p> Signup and view all the answers

What is the final step in the process of creating new virions within a host cell?

<p>Budding</p> Signup and view all the answers

What is the term used for medication given to HIV-negative individuals after potential exposure to the virus?

<p>Post-exposure prophylaxis (PEP)</p> Signup and view all the answers

What is the primary high-risk situation for HIV transmission that is often mentioned for preventive measures?

<p>Unprotected sex</p> Signup and view all the answers

What is the term for medication given to individuals with increased risk of HIV infection before potential exposure?

<p>Pre-exposure prophylaxis (PrEP)</p> Signup and view all the answers

What is the key challenge mentioned in the text regarding the development of a vaccine for HIV?

<p>There is currently no vaccine available for HIV</p> Signup and view all the answers

Which viral protein binds to CD4 on the host membrane and tags it with ubiquitin for removal?

<p>Vpu</p> Signup and view all the answers

What type of nucleic acid does the HIV virus contain?

<p>Single-stranded RNA</p> Signup and view all the answers

What is the ideal target for HIV drug therapy?

<p>Reverse transcriptase</p> Signup and view all the answers

What is the mechanism of action of Zidovudine (AZT)?

<p>Inhibits reverse transcriptase and acts as a chain terminator.</p> Signup and view all the answers

What was the second HIV drug approved in the USA?

<p>Didanosine (DdI)</p> Signup and view all the answers

What are the two drugs generated by replacing the 3' carbon with a sulfur atom?

<p>Lamivudine and Emtricitabine</p> Signup and view all the answers

Name the only guanosine analogue among the clinically useful NRTIs.

<p>Abacavir</p> Signup and view all the answers

What is the base of Stavudine, a thymidine analogue?

<p>Thymidine</p> Signup and view all the answers

What is the base of Zalcitabine, a cytosine analogue?

<p>Cytosine</p> Signup and view all the answers

What is the common mechanism of action for Nucleoside reverse transcriptase inhibitors (NRTIs)?

<p>They all need to be triphosphorylated for activity.</p> Signup and view all the answers

Why do NRTIs require triphosphorylation for activity?

<p>HIV lacks viral thymidine kinase, so all 3 phosphorylations must be cellular.</p> Signup and view all the answers

What is the role of prodrugs like Adefovir and Tenofovir in NRTI therapy?

<p>They are adenosine analogues that are converted to the active triphosphate version.</p> Signup and view all the answers

What are the two main components of combination therapy for HIV mentioned in the text?

<p>Emtricitabine and Cobcistat</p> Signup and view all the answers

What is the mechanism of action of NNRTIs?

<p>Non-competitive, reversible inhibition</p> Signup and view all the answers

What is the main issue mentioned with Delavirdine?

<p>Mutation of Pro-236 leading to resistance</p> Signup and view all the answers

How do 2nd generation NNRTIs interact with the binding pocket?

<p>Non-aromatic moiety interacts with aromatic residues at the top of the binding pocket</p> Signup and view all the answers

What is the main benefit of administering PIs and RTIs together?

<p>Enhanced viral activity and slower development of viral resistance</p> Signup and view all the answers

Why are PIs different from RTIs in terms of activation?

<p>PIs are not prodrugs and do not require activation</p> Signup and view all the answers

What is the main challenge faced in developing PIs from peptide lead compounds?

<p>Reducing peptidic character while maintaining activity and gaining oral bioavailability</p> Signup and view all the answers

What are the two binding sites distinct from each other mentioned in the text?

<p>NRTI and NNRTI binding sites</p> Signup and view all the answers

What feature distinguishes Nevirapine and Delavirdine from other NNRTIs mentioned in the text?

<p>Chiral and larger size, respectively</p> Signup and view all the answers

What is the role of X-ray crystallography in designing inhibitors for viral HIV protease?

<p>Structure-based design of inhibitors</p> Signup and view all the answers

How does the combination of multiple drugs in HAART therapy help minimize the risk of resistance?

<p>By decreasing the chance of mutation leading to resistance for each drug</p> Signup and view all the answers

What is the probability of developing resistance when taking 3 drugs with a mutation chance of 1:10,000 for each drug?

<p>1 in a trillion chance of resistance</p> Signup and view all the answers

Why is patient compliance important in HIV treatment?

<p>To ensure the effectiveness of the treatment and minimize the risk of resistance</p> Signup and view all the answers

What are the three classes of drugs commonly used in HIV treatment?

<p>Protease inhibitors, Nucleoside Reverse transcriptase inhibitors, Non-nucleoside Reverse transcriptase inhibitors</p> Signup and view all the answers

What is the main function of Protease Inhibitors (PIs) in HIV treatment?

<p>To interfere with the preparation of the virion</p> Signup and view all the answers

Why is a combined HAART approach considered more effective than a single drug approach in HIV treatment?

<p>To prevent the development of resistance and maintain treatment efficacy</p> Signup and view all the answers

What is the role of the HIV protease enzyme in the HIV life cycle?

<p>To cleave peptide bonds in the non-functional polyproteins to produce mature viral proteins for budding.</p> Signup and view all the answers

Why is the interface between two protein units of the HIV protease enzyme important?

<p>It contains the active site where peptide bonds are cleaved.</p> Signup and view all the answers

What gives the HIV protease enzyme specificity for the virus rather than the cell?

<p>The symmetry of its active site, which is not present in mammalian proteases.</p> Signup and view all the answers

How many variants of HIV protease exist and what is the sequence match between them?

<p>Two variants exist with a 50% sequence match.</p> Signup and view all the answers

What is the purpose of inhibitors binding to both variants of HIV protease?

<p>To ensure effectiveness against both variants despite their sequence differences.</p> Signup and view all the answers

What is the significance of introducing stable tetrahedral features in designing HIV-Protease inhibitors?

<p>It mimics the tetrahedral stereochemistry of the transition state and is likely to bind more strongly than substrate or product.</p> Signup and view all the answers

Why is the hydroxyethylamine isostere considered effective in designing HIV-Protease inhibitors?

<p>It mimics one of the hydroxyls in the transition state and has been proven to be effective.</p> Signup and view all the answers

What is the role of Asp-25, Thr-26, and Gly-27 in the active site of the HIV protease enzyme?

<p>They form the bottom of the active site where peptide bonds are cleaved.</p> Signup and view all the answers

How many binding subsites are available for amino acid side chains in HIV-Protease?

<p>There are 8 binding subsites (S4-S4').</p> Signup and view all the answers

Why is the broad substrate specificity of the HIV protease enzyme significant?

<p>It allows cleavage of a variety of peptide bonds, including those not cleaved by known mammalian proteases.</p> Signup and view all the answers

What are the desirable features of HIV-Protease Inhibitors?

<p>Keep MWt low, good oral bioavailability, good water solubility, selective for viral protease, activity unaltered by mutation of viral protease</p> Signup and view all the answers

What are the disadvantages associated with Saquinavir?

<p>High molecular weight, high peptide character, poor oral bioavailability</p> Signup and view all the answers

How was Saquinavir modified to simplify its structure and improve its features?

<p>Start from a dipeptide rather than a pentapeptide</p> Signup and view all the answers

What was the lead compound used to design Tipranavir?

<p>Non-peptide lead compound</p> Signup and view all the answers

What is the significance of the transition state isostere in the design of Saquinavir?

<p>Interacts with the catalytic aspartates, improves activity</p> Signup and view all the answers

How did the design strategy differ between Ritonavir (1st generation) and Lopinavir (2nd generation)?

<p>Ritonavir designed to take advantage of symmetry, Lopinavir derived from ritonavir</p> Signup and view all the answers

Which modern protease inhibitor aims to increase metabolic stability compared to precursor analogues?

<p>Tipranavir</p> Signup and view all the answers

What compound showed weak protease inhibition but analogues like Phenprocoumon were more active with good oral bioavailability?

<p>Warfarin</p> Signup and view all the answers

What are some key features to consider in the design of protease inhibitors?

<p>Transition state isostere, interaction with subsites, small size, solubility, bioisosteres, metabolic stability</p> Signup and view all the answers

Why is it important to start small and build up in the design of HIV-Protease Inhibitors?

<p>To maximize key interactions, improve solubility, and avoid mutation issues</p> Signup and view all the answers

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