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Anti viral agents ppt
- 1. ANTI VIRAL AGENTS MS.NAVDHA SONI ASST. PROFESSOR L.J INSTITUTE OF PHARMACY 1
- 2. STRUCTURE OF VIRUS Virusdoesn’t possess cell wall. It consists of one or more of linear or helical strands pf either DNA or RNA, enclosed in the shell of protein known as capsid. The capsid is composed of several sub units known as capsomers. In certain cases, capsid may be surrounded by an outer protein or lipoprotein envelop. INTRODUCTION 2 Anti viral drugs are a class of medication used specifically for treating viral infections.Viruses are obligate intracellular parasites, smallest of all self replicating organisms, able to pass through filter that retain the smallest bacteria.Virus conduct no metabolic process on their own.They invade the host cell which may be bacteria, animal or plant cell.
- 3. VIRAL REPLICATION • Adsorptionand penetration into susceptible host cells. • Un coating of viral nucleic acid • Synthesis of early regulatory proteins • Synthesis of RNA or DNA • Synthesis of late regulatory proteins • Assembly (maturation) of viral particles • Release from cells 3
- 4. WHY VIRAL THERAPYIS DIFFICULT? • Viruses are essentially intracellular parasite. Unlike bacteria, the viral replication is totally dependent upon the energy, protein and enzymatic machinery of the host cell. • Bacteria have self contained biosynthetic machinery. Hence the drug in bacterial chemotherapy enjoy the advantage of selective attack on bacteria due to many metabolic and molecular differences between the pathogens and the host cells. Since viruses literally take over the metabolic machinery of the infected human cell, A close relationship exists between the multiplying the virus and the host cell. • Virus replication is intimately dependent upon the host cell metabolism. This fact severely limits the usual opportunities to design antiviral agent having selective effect on the viral cell. Attempts to inhibit viral growth without damaging the host cell became fruitless. • Viruses pose a considerable challenge to the body’s immune system because they hide inside cells. This makes it difficult for antibodies to reach them. Some special immune system cells, called T-lymphocytes, can recognise and kill cells containing viruses, since the surface of infected cells is changed when the virus begins to multiply. 4
- 5. WHY VIRAL THERAPYIS DIFFICULT? • Many viruses, when released from infected cells, will be effectively knocked out by antibodies that have been produced in response to infection or previous immunisation. • Antibiotics are useless against viral infections. This is because viruses are so simple that they use their host cells to perform their activities for them. So antiviral drugs work differently to antibiotics, by interfering with the viral enzymes instead. • Antiviral drugs are currently only effective against a few viral diseases, such as influenza, herpes, hepatitis B and C and HIV – but research is ongoing. A naturally occurring protein, called interferon (which the body produces to help fight viral infections), can now be produced in the laboratory and is used to treat hepatitis C infections. 5
- 6. CLASSIFICATION A. Purine nucleosides& nucleotides B. Pyrimidine nucleosides & nucleotides C. Thiosemicarbazones D. Benzimidazoles E. Admantane amines F. Interferones G. Miscellaneous agents 6
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- 8. ACYCLOVIR MECHANISM OF ACTION: Acyclovirgets activated after three phosphorylation steps by viral specific enzymes termed thymidine kinases.These active metabolites accumulate in the infected cells and exerts their action by two mechanisms. • Competitive inhibition of herpes virus DNA polymerases • Incorporation of Acyclovir into viral DNA USES: It is a drug of choice in both prophylaxis and treatment of herpes simplex virus, particularly type-1 including chronic and recurrent mucocutaneous herpes in the immunologically impaired host, primary and secondary genital herpes and herpes simplex encephalitis.Cells infected with herpex simplex phosphorylate the drug to yield a cycloguanosine triphosphate, which preferentially inhibits viral DNA polymerase. 8
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- 11. IDOXURIDINE MECHANISM OF ACTION: Idoxuridineacts as an anti viral agent against DNA virus. It is phosphorylated by thymidine kinase to active triphosphate. This phosphorylated drug inhibits Herpes Simplex Virus(HSV) DNA polymerase enzyme which is necessary for the synthesis of viral DNA. The ability of idoxuridylic acid substitute for deoxythymidic acid in the synthesis of viral DNA may be due to the similar vander waal’s radii of iodine and the thymidine methyl group. USES: Idoxuridine is mainly used for the topical treatment of HSV infection of eyelid, conjuctiva & cornea and approved as ophthalmic ointment or solution. Epithelial infections respond much better than stromal infections. 11
- 12. C. THIOSEMICARBAZONES Methisazone MECHANISM OFACTION: The antiviral action of Thiosemicarbazones is perhaps due to the formation of metal chelates with various metal ions including Cu, Zn, Ni, Fe & Mn. Methisazone thus acts by interacting with metalloenzymes that are necessary for the replication of certain viruses. The Thiosemicarbazones may also react directly and specifically with viral nucleic acid. USES: It is used as a prophylactic agent against small pox & for the prevention and treatment of generalised vaccinia or vaccinial encephalicis. 12
- 13. D. BENZIMIDAZOLES MECHANISM OFACTION: It is an enhancer of interferon induction, A possible result of inhibition of interferon RNA synthesis of the shut off of interferon production. USES: It appears to act by inhibition of viral RNA synthesis. 13
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- 15. AMANTADINE USES: Amantadine is awhite, odourless, crystalline powder with a bitter taste, freely soluble in water. It is effective in the prophylaxis and therapy of infection caused by influenza-A and is active against a number of DNA and RNA virus in vitro.It may block either the assembly of influenza-A virus or the release of viral nucleic acid in the host cell. The drug is well absorbed from the GIT is not metabolised and is excreted by the kidney. Dose related adverse effects include confusion, hallucinations, seizures & coma. MECHANISM OF ACTION: It allows viral adsorption to the host cell but inhibits the uncoating of influenza virus and prohibits penetration of viral genome into the host cell because the virion remains adsorbed to the host cell surface it become susceptible to attack by host anti bodies. 15
- 16. F. INTERFERONES The interferons(IFNs) are glycoproteins with strong antiviral activities that represent one of the first lines of host defense against invading pathogens. These proteins are classified into three groups, Type I, II and III IFNs, based on the structure of their receptors on the cell surface. Due to their ability to modulate immune responses, they have become attractive therapeutic options to control chronic virus infections. In combination with other drugs, Type I IFNs are considered a “standard of care” in suppressing Hepatitis C (HCV) and Hepatitis B (HBV) infections, while Type III IFN has generated encouraging results as a treatment for HCV infection in phase III clinical trials. However, though effective, using IFNs as a treatment is not without the need for caution. IFNs are such powerful cytokines that affect a wide array of cell types; as a result, patients usually experience unpleasant symptoms, with a percentage of patients suffering system wide effects. 16
- 17. F. INTERFERONES Thus, constantmonitoring is required for patients treated with IFN in order to reach the treatment goals of suppressing virus infection and maintaining quality of life. Interferon synthesis and liberation in animal can be induced by 1. Biological Inducer: These include human Leukocytes, fibroblasts or lymphoblastoid cells. 2. Chemical Inducers: These include polyriboinosinic polyribocytidilic acid (Synthetic analog of double stranded RNA), group of 6-phenylpyrimidine derivative & Tilorone hydrochloride 17
- 18. G. MISCELLANEOUS AGENTS 1.Ureas and Thioureas 2. Guanidines and Biguanidines 3. Heterocyclic Dyes 4. Gamma Globulines 5. Antibiotics 6. Other investigational anti Viral Drugs 18
- 19. HIV CELL ANDLIFE CYCLE: ANTIRETROVIRAL AGENTS 19
- 20. CLASSIFICATION ART DRUGS A.Nucleosides Reverse Transcriptase Inhibitors (NRTIs) B. Non Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) C. Protease Inhibitors D. Entry Inhibitors (CCR5 receptor antagonist) E. Integrase Inhibitors F. Fusion Inhibitors 20
- 21. A. NRTIS • Firstagents available for HIV Infection • Less potent than NNRTIs and Protease Inhibitors • Have a central role in ART • Have activity against HIV-1 and HIV-2. • Nucleoside and nucleotide an analogues • Differ from normal substrates only by a minor modification in sugar (ribose) molecule Lamivudine Zalcitabine Didanosine 21
- 22. A. NRTIS MECHANISM OFACTION: • Interrupt HIV replication cycle via competitive inhibition of HIV reverse transcriptase and termination of the DNA chain • Reverse transcriptase. • An HIV-specific DNA polymerase • Allows HIV RNA to be transcribed into ss and ultimately dsproviral DNA and incorporated into host-cell genome. • Proviral DNA chain elongation is necessary before genome incorporation can occur • Acting as "false building blocks causes Chain termination, • Once incorporated, work by preventing other nucleosides from also being incorporated b/c of absence of a 3’ OH group. 22
- 23. B. NNRTIS • Wereintroduced in 1996 with approval of nevirapine. • Have potent activity against HIV-1 and are part of preferred initial regimens. • Efavirenz, confers most significant inhibition of viral infectivity • All exhibit same mechanism of action Delaviridine Loviride 23
- 24. B. NNRTIS MECHANISM OFACTION: • HIV reverse transcriptase is a heterodimer composed of 2 subunits (p66 and p51). • NNRTIs bind p66 subunit at a hydrophobic pocket distant from active site of enzyme (allosteric site). • This noncompetitive binding induces a conformational change in enzyme. • 1st generation NNRTIs are more rigid in structure. • Resistance can quickly be developed. • 2nd generation NNRTIs have a more flexible structure. • Adjust readily and resist mutation more effectively. 24
- 25. C. PROTEASE INHIBITORS •First introduced in 1995 • Are an integral part of treatment • Exhibit activity against clinical isolates of both HIV-1 and HIV-2. IndinavirRitonavir 25
- 26. C. PROTEASE INHIBITORS MECHANISMOF ACTION: • HIV protease is a 99-amino-acid, aspartic acid protein. • Responsible for maturation of virus particles late in viral life cycle. • Systematically cleaves individual proteins from gag and gag-pol polypeptide precursors into functional subunits for viral capsid formation during or shortly after viral budding from an infected cell. • Competitive inhibitors. • Directly bind to HIV protease and prevent subsequent cleavage of polypeptides. 26
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