Lecture+8_+Ch+30.3-30.4+Prevention+and+treatment (1).pdf

Chapter 30.3: Pathogenesis and Control of Viral Diseases Twenty-Eighth Edition Jawetz, Melnick, & Adelberg’s Medical Microbiology...

Chapter 30.3: Pathogenesis and Control of Viral Diseases Twenty-Eighth Edition Jawetz, Melnick, & Adelberg’s Medical Microbiology Twenty-Eighth Edition Stefan Riedel Slides by Dr. Jose Sapien Jawetz, Melnick, & Adelberg’s Medical Microbiology, Twenty-Eighth Edition Copyright © McGraw Hill 30.3: Prevention and Treatment Of Viral Infections Antiviral Chemotherapy Antiviral development can be challenging due to viruses being obligate intracellular parasites When creating antivirals: Selectively inhibit viral function. Virus replication during the incubation period make it hard to time start of tx. Successful drugs are mainly for chronic infections © McGraw-Hill Education, 2019  A review: Mechanism of action of antiviral drugs - PMC (nih.gov) Antiviral Drugs Need to create effective antivirals for viruses when there are no vaccines available due to multiple serotypes (rhinoviruses = 160) or constant changing viral antigens (influenza, HIV). Reduce morbidity and economic loss Treatment for immunocompromised patients at risk for severe disease Options for targets: attachment, uncoating, viral nucleic acid synthesis, translation of viral proteins and progeny virus assembly Main difficulty: antiviral that can distinguish between host and viral replicative processes © McGraw-Hill Education, 2019 © McGraw-Hill Education, 2019  30.3: Prevention and Treatment Of Viral Infections A. Nucleoside and Nucleotide Analogs Majority of antiviral agents are nucleoside analogs: Mimic physiological endogenous nucleosides Synthetically made and chemically modified Block cellular division or replication by impairing DNA/RNA synthesis Inhibit viral enzymes for making nucleosides Nucleoside analogs as a rich source of antiviral agents active against arthropod- borne flaviviruses - PMC (nih.gov) © McGraw-Hill Education, 2019 30.3: Prevention and Treatment Of Viral Infections B. Reverse Transcriptase Inhibitors Nonnucleoside reverse transcriptase inhibitors: Act by binding directly to virally encoded reverse transcriptase = stops activity Resistant mutants can emerge quickly Usually used in multidrug therapies © McGraw-Hill Education, 2019  30.3: Prevention and Treatment Of Viral Infections C. Protease Inhibitors Used successfully for treating HIV and HCV infections Peptidomimetic agents → fit into active site of HIV protease enzyme: Blocks the viral protease for the last stage of replicative cycle → inhibit cleave specific precursors (gag & gag pol) for formation of mature virion core Stops Activation of the reverse transcriptase used in next round of infection © McGraw-Hill Education, 2019  30.3: Prevention and Treatment Of Viral Infections D. Integrase Inhibitors & Fusion inhibitors HIV Integrase inhibitors block activity of viral integrase → stopping lifecycle (Raltegravir) From: https://viralzone.expasy.org/5156 © McGraw-Hill Education, 2019 E. HIV fusion inhibitors They act by disrupting fusion of viral envelope with cell membrane → stops cellular infection. Enfuvirtide is a peptide that binds to gp41 → blocks the required conformational change → no membrane fusion. From: https://clinicalinfo.hiv.gov/sites/default/files/glossary/Glossary-English_HIVinfo.pdf © McGraw-Hill Education, 2019 From: https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_%28Boundless%29/09%3A_Viruses/9.10%3A_Retroviruses-_Double- © McGraw-Hill Education, 2019 Stranded_RNA_Viruses/9.10B%3A_HIV_Attachment_and_Host_Cell_Entry  30.3: Prevention and Treatment Of Viral Infections F. Other Types of Antiviral Agents More antivirals, but need certain conditions Amantadine & rimantadine: need early administration for effect on blocking influenza A uncoating Oseltamivir is a neuraminidase inhibitor- stops release of influenza particles Acyclovir is a guanosine analog DNA polymerase inhibitor used in HSV and varicella-zoster treatment © McGraw-Hill Education, 2019 30.3: Prevention and Treatment Of Viral Infections Viral Vaccines Why get a vaccine? To use the adaptive immune response to prevent viral disease Many very effective vaccines Most cost-effective method to prevent serious infection © McGraw-Hill Education, 2019  30.3: Prevention and Treatment Of Viral Infections A. General Principles Development of immune response to specific antigens. Enveloped viruses: glycoproteins. A guide to vaccinology: from basic principles to new developments | Nature Reviews Immunology © McGraw-Hill Education, 2019 General Principles Pathogenesis influences immunoprophylaxis (prevention of disease). IgA (mucosal immunity) contributes to resistance of viruses that replicate in mucosal surfaces (rhinoviruses, influenza viruses, rotaviruses) or invade through mucosa (HPV) IgG (in serum) antibodies contribute to resistance of viremic viruses (polio, hepatitis A and B, yellow fever, varicella). © McGraw-Hill Education, 2019 Viral Vaccines approved in US © McGraw-Hill Education, 2019 Complications in making effective vaccines arise when: Several serotypes (rhinoviruses) Large number of antigenic varients in animal resevoirs (influenza) If a virus integrates into host DNA (retroviruses) Infects immune system (HIV) Fig. 5: Influenza antigenic shift and antigenic drift. | Nature Reviews Disease Primers © McGraw-Hill Education, 2019 30.3: Prevention and Treatment Of Viral Infections B. Killed-Virus Vaccines Inactivating vaccines (purifying & inactivating viral infectivity). Some viruses only have this form of vaccine available. Advantages : No reversion to virulence. Vaccine can be made when no attenuated available. Disadvantage: Only have a brief immunity (need boosters). Hypersensitivity to subsequent infection © McGraw-Hill Education, 2019 30.3: Prevention and Treatment Of Viral Infections C. Attenuated Live-Virus Vaccines Use virus mutants that antigenically overlap with wild-type virus. Key: restricted in a step of pathogenesis of disease © McGraw-Hill Education, 2019 Attenuated Live-Virus Advantage: Disadvantages: Act more like natural infection Risk of reversion to (better built immunity) greater virulence Longer lasting antibody Sever infection in production immunocompromised hosts Good cell-mediated response Limited shelf life Induce antibody production (sometimes) and resistance at portal of entry © McGraw-Hill Education, 2019 30.3: Prevention and Treatment Of Viral Infections D. Proper Use of Vaccines Need: Proper dosage to susceptible individuals. All sectors of population get immunized for herd immunity. Herd immunity: risk of infection among susceptible individuals is reduced by adequate numbers of immune people. © McGraw-Hill Education, 2019  Summary Selective Inhibition: Effective antiviral medications are designed to specifically target viral functions without interfering with cellular processes. Antivirals classification is based on their function. Vaccination for Prevention: Vaccines remain the most effective strategy for preventing viral infections, with options available for several significant viral diseases. Types of Vaccines: Both inactivated (killed) and live attenuated vaccines are utilized, each offering distinct advantages and drawbacks. © McGraw-Hill Education, 2019 Questions? © McGraw-Hill Education, 2019