1. 14. Viruses prof. aza

2. 14. Viruses Viruses are infective agents that are considerably smaller than bacteria. They are essentially packages, known as virions, of chemicals that invade host cells. Viruses are infective agents that are considerably smaller than bacteria. They are essentially packages, known as virions, of chemicals that invade host cells. However, viruses are not independent and can only penetrate a host cell that can satisfy the specific needs of that virus. However, viruses are not independent and can only penetrate a host cell that can satisfy the specific needs of that virus. prof. aza

3. The mode of penetration varies considerably from virus to virus. Once inside the host cell viruses take over the metabolic machinery of the host and use it to produce more viruses. Replication is often lethal to the host cell, which may undergo lysis to release the progeny of the virus. The mode of penetration varies considerably from virus to virus. Once inside the host cell viruses take over the metabolic machinery of the host and use it to produce more viruses. Replication is often lethal to the host cell, which may undergo lysis to release the progeny of the virus. prof. aza

4. However, in some cases the virus may integrate into the host chromosome and become dormant. The ability of viruses to reproduce means that they can be regarded as being on the borderline of being living organisms. However, in some cases the virus may integrate into the host chromosome and become dormant. The ability of viruses to reproduce means that they can be regarded as being on the borderline of being living organisms. prof. aza

5. 14.1. Structure and replication Viruses consist of a core of either DNA or, as in the majority of cases, RNA fully or partially covered by a protein coating known as the capsid. The capsid consists of a number of polypeptide molecules known as capsomers (Fig.10.43). Viruses consist of a core of either DNA or, as in the majority of cases, RNA fully or partially covered by a protein coating known as the capsid. The capsid consists of a number of polypeptide molecules known as capsomers (Fig.10.43). prof. aza

6. Figure 10.37. (a) Schematic representations of the structure of a virus (a) without a lipoprotein envelope (naked virus) and (b) with a lipoprotein envelope.

7. The capsid that surrounds most viruses consists of a number of different capsomers although some viruses will have capsids that only contain one type of capsomer. The capsid that surrounds most viruses consists of a number of different capsomers although some viruses will have capsids that only contain one type of capsomer. It is the arrangement of the capsomers around the nucleic acid that determines the overall shape of the virion. It is the arrangement of the capsomers around the nucleic acid that determines the overall shape of the virion. prof. aza

8. In the majority of viruses, the capsomers form a layer or several layers that completely surround the nucleic acids. However, there are some viruses in which the capsomers form an open-ended tube that holds the nucleic acids. In the majority of viruses, the capsomers form a layer or several layers that completely surround the nucleic acids. However, there are some viruses in which the capsomers form an open-ended tube that holds the nucleic acids. prof. aza

9. In many viruses the capsid is coated with a protein-containing lipid bilayer membrane. In many viruses the capsid is coated with a protein-containing lipid bilayer membrane. These are known as enveloped viruses. Their lipid bilayers are often derived from the plasma membrane of the host cell and are formed when the virus leaves the host cell by a process known as budding. These are known as enveloped viruses. Their lipid bilayers are often derived from the plasma membrane of the host cell and are formed when the virus leaves the host cell by a process known as budding. prof. aza

10. Budding is a mechanism by which a virus leaves a host cell without killing that cell. It provides the virus with a membrane whose lipid components are identical to those of the host (Fig. 10.43). Budding is a mechanism by which a virus leaves a host cell without killing that cell. It provides the virus with a membrane whose lipid components are identical to those of the host (Fig. 10.43). This allows the virus to penetrate new host cells without activating the host’s, immune systems. This allows the virus to penetrate new host cells without activating the host’s, immune systems. prof. aza

11. Viruses bind to host cells at specific receptor sites on the host’s cell envelope. Viruses bind to host cells at specific receptor sites on the host’s cell envelope. The binding sites on the virus are polypeptides in its capsid or lipoprotein envelope. Once the virus has bound to the receptor of the host cell the virus– receptor complex is transported into the cell by receptor-mediated endocytosis. The binding sites on the virus are polypeptides in its capsid or lipoprotein envelope. Once the virus has bound to the receptor of the host cell the virus– receptor complex is transported into the cell by receptor-mediated endocytosis. prof. aza

12. In the course of this process the protein capsid and any lipoprotein envelopes may be removed. In the course of this process the protein capsid and any lipoprotein envelopes may be removed. Once it has entered the host cell the viral nucleic acid is able to use the host’s cellular machinery to synthesise the nucleic acids and proteins required to replicate a number of new viruses (Fig. 10.44). Once it has entered the host cell the viral nucleic acid is able to use the host’s cellular machinery to synthesise the nucleic acids and proteins required to replicate a number of new viruses (Fig. 10.44). prof. aza

13. A great deal of information is available concerning the details of the mechanism of virus replication but this text will only outline the main points. For greater detail the reader is referred to specialist texts on virology. A great deal of information is available concerning the details of the mechanism of virus replication but this text will only outline the main points. For greater detail the reader is referred to specialist texts on virology. prof. aza

14. 14.2. Classification RNA-viruses can be broadly classified into two general types, namely: RNA-viruses and RNA-retroviruses. RNA-viruses can be broadly classified into two general types, namely: RNA-viruses and RNA-retroviruses. prof. aza

15. Figure 10.44 A schematic representation of the replication of RNA-viruses Figure 10.44 A schematic representation of the replication of RNA-viruses prof. aza

16. RNA-viruses RNA-virus replication usually occurs entirely in the cytoplasm. The viral mRNA either forms part of the RNA carried by the virion or is synthesised by an enzyme already present in the virion. RNA-virus replication usually occurs entirely in the cytoplasm. The viral mRNA either forms part of the RNA carried by the virion or is synthesised by an enzyme already present in the virion. prof. aza

17. This viral mRNA is used to produce the necessary viral proteins by translation using the host cell’s ribosomes and enzyme systems. This viral mRNA is used to produce the necessary viral proteins by translation using the host cell’s ribosomes and enzyme systems. prof. aza

18. Some of the viral proteins are enzymes that are used to catalyse the reproduction of more viral mRNA. The new viral RNA and viral proteins are assembled into a number of new virions that are ultimately released from the host cell by either lysis or budding. Some of the viral proteins are enzymes that are used to catalyse the reproduction of more viral mRNA. The new viral RNA and viral proteins are assembled into a number of new virions that are ultimately released from the host cell by either lysis or budding. prof. aza

19. Retroviruses Retroviruses synthesise viral DNA using their viral RNA as a template. Retroviruses synthesise viral DNA using their viral RNA as a template. This process is catalysed by enzyme systems known as reverse transcriptases that form part of the virion. The viral DNA is incorporated into the host genome to form a so- called provirus. This process is catalysed by enzyme systems known as reverse transcriptases that form part of the virion. The viral DNA is incorporated into the host genome to form a so- called provirus. prof. aza

20. Transcription of the provirus produces new ‘genomic’ viral RNA and viral mRNA. The viral mRNA is used to produce viral proteins, which together with the ‘genomic’ viral RNA are assembled into new virions. Transcription of the provirus produces new ‘genomic’ viral RNA and viral mRNA. The viral mRNA is used to produce viral proteins, which together with the ‘genomic’ viral RNA are assembled into new virions. prof. aza

21. These virions are released by budding, which in many cases does not kill the host cell. Retroviruses are responsible for some forms of cancer and AIDS These virions are released by budding, which in many cases does not kill the host cell. Retroviruses are responsible for some forms of cancer and AIDS prof. aza

22. DNA-viruses Most DNA-viruses enter the host cell’s nucleus where formation of viral mRNA by transcription from the viral DNA is brought about by the host cell’s polymerases. This viral mRNA is used to produce viral proteins by translation using the host cell’s ribosomes and enzyme systems. Most DNA-viruses enter the host cell’s nucleus where formation of viral mRNA by transcription from the viral DNA is brought about by the host cell’s polymerases. This viral mRNA is used to produce viral proteins by translation using the host cell’s ribosomes and enzyme systems. prof. aza

23. Some of these proteins will be enzymes that can catalyse the synthesis of more viral DNA. Some of these proteins will be enzymes that can catalyse the synthesis of more viral DNA. This DNA and the viral proteins synthesised in the host cell are assembled into a number of new virions that are ultimately released from the host by either cell lysis or budding This DNA and the viral proteins synthesised in the host cell are assembled into a number of new virions that are ultimately released from the host by either cell lysis or budding prof. aza

24. 14.3. Viral diseases Viral infection of host cells is a common occurrence. Most of the time this infection does not result in illness as the body’s immune system can usually deal with such viral invasion. Viral infection of host cells is a common occurrence. Most of the time this infection does not result in illness as the body’s immune system can usually deal with such viral invasion. When illness occurs it is often short lived and leads to long-term immunity. When illness occurs it is often short lived and leads to long-term immunity. prof. aza

25. However, a number of viral infections can lead to serious medical conditions (. Some viruses like HIV, the aetiological agent of AIDS, are able to remain dormant in the host for a number of years before becoming active, whilst others such as herpes zoster (shingles) can give rise to recurrent bouts of the illness. Both chemotherapy and preventative However, a number of viral infections can lead to serious medical conditions (. Some viruses like HIV, the aetiological agent of AIDS, are able to remain dormant in the host for a number of years before becoming active, whilst others such as herpes zoster (shingles) can give rise to recurrent bouts of the illness. Both chemotherapy and preventative vaccination are used to treat patients. The latter is the main clinical approach since it has vaccination are used to treat patients. The latter is the main clinical approach since it has been difficult to design drugs that only target the virus. However, a number of antiviral been difficult to design drugs that only target the virus. However, a number of antiviral drugs have been developed and are in clinical use. drugs have been developed and are in clinical use. AIDS AIDS prof. aza

26. Both chemotherapy and preventative vaccination are used to treat patients. The latter is the main clinical approach since it has been difficult to design drugs that only target the virus. However, a number of antiviral drugs have been developed and are in clinical use. Both chemotherapy and preventative vaccination are used to treat patients. The latter is the main clinical approach since it has been difficult to design drugs that only target the virus. However, a number of antiviral drugs have been developed and are in clinical use. prof. aza

28. AIDS AIDS is a disease that progressively destroys the human immune system. It is caused by the human immunodeficiency virus (HIV), which is a retrovirus. This virus enters and destroys human T4 lymphocyte cells. These cells are a vital part of the human immune system. AIDS is a disease that progressively destroys the human immune system. It is caused by the human immunodeficiency virus (HIV), which is a retrovirus. This virus enters and destroys human T4 lymphocyte cells. These cells are a vital part of the human immune system. prof. aza

29. Their destruction reduces the body’s resistance to other infectious diseases, such as pneumonia, and some rare forms of cancer. Their destruction reduces the body’s resistance to other infectious diseases, such as pneumonia, and some rare forms of cancer.. prof. aza

30. The entry of the virus into the body usually causes an initial period of acute ill health with the patient suffering from headaches, fevers and rashes, amongst other symptoms. The entry of the virus into the body usually causes an initial period of acute ill health with the patient suffering from headaches, fevers and rashes, amongst other symptoms. This is followed by a period of relatively good healthy where the virus replicates in the lymph nodes. This is followed by a period of relatively good healthy where the virus replicates in the lymph nodes. prof. aza

31. This relatively healthy period normally lasts a number of years before fullblown This relatively healthy period normally lasts a number of years before fullblown AIDS appears. Full-blown AIDS is characterised by a wide variety of diseases such as bacterial infections, neurological diseases and cancers. Treatment is more effective when a mixture of antiviral agents is used AIDS appears. Full-blown AIDS is characterised by a wide variety of diseases such as bacterial infections, neurological diseases and cancers. Treatment is more effective when a mixture of antiviral agents is used prof. aza

32. 14.4. Antiviral drugs It has been found that viruses utilize a number of virus-specific enzymes during replication. It has been found that viruses utilize a number of virus-specific enzymes during replication. These enzymes and the processes they control are significantly different from those of the host cell to make them a useful target for medicinal chemists. These enzymes and the processes they control are significantly different from those of the host cell to make them a useful target for medicinal chemists. prof. aza

33. Consequently, antiviral drugs normally act by : Consequently, antiviral drugs normally act by : inhibiting viral nucleic acid synthesis, inhibiting viral nucleic acid synthesis, inhibiting attachment to and penetration of the host cell or inhibiting attachment to and penetration of the host cell or inhibiting viral protein synthesis. inhibiting viral protein synthesis. prof. aza

34. Nucleic acid synthesis inhibitors Nucleic acid synthesis inhibitors usually act by inhibiting the polymerases or reverse transcriptases required for nucleic acid chain formation. Nucleic acid synthesis inhibitors usually act by inhibiting the polymerases or reverse transcriptases required for nucleic acid chain formation. However, because they are usually analogues of the purine and pyrimidine bases found in the viral nucleic acids, they are often incorporated into the growing nucleic acid chain. However, because they are usually analogues of the purine and pyrimidine bases found in the viral nucleic acids, they are often incorporated into the growing nucleic acid chain. prof. aza

35. In this case their general mode of action frequently involves conversion to the corresponding 5-triphosphate by the host cell’s cellular kinases. In this case their general mode of action frequently involves conversion to the corresponding 5-triphosphate by the host cell’s cellular kinases. This conversion may also involve specific viral enzymes in the initial monophosphorylation step. This conversion may also involve specific viral enzymes in the initial monophosphorylation step. prof. aza

36. These triphosphate drug derivatives are incorporated into the nucleic acid chain where they terminate its formation. Termination occurs because the drug residues do not have the 3-hydroxy group necessary for the phosphate ester formation required for further growth of the nucleic acid chain. These triphosphate drug derivatives are incorporated into the nucleic acid chain where they terminate its formation. Termination occurs because the drug residues do not have the 3-hydroxy group necessary for the phosphate ester formation required for further growth of the nucleic acid chain. prof. aza

37. This effectively inhibits the polymerases and transcriptases that catalyze the growth of the nucleic acid (Fig. 10.45). This effectively inhibits the polymerases and transcriptases that catalyze the growth of the nucleic acid (Fig. 10.45). prof. aza

39. Aciclovir Aciclovir was the first effective antiviral drug. It is effective against a number of herpes viruses, notably simplex, varicella-zoster (shingles), varicella (chickenpox) and Epstein–Barr virus (glandular fever). Aciclovir was the first effective antiviral drug. It is effective against a number of herpes viruses, notably simplex, varicella-zoster (shingles), varicella (chickenpox) and Epstein–Barr virus (glandular fever). It may be administered orally and by intravenous injection as well as topically. Orally administered doses have a low bioavailability. It may be administered orally and by intravenous injection as well as topically. Orally administered doses have a low bioavailability. prof. aza

40. The action of aciclovir is more effective in virus-infected host cells because the viral thymidine kinase is a more efficient catalyst for the monophosphorylation of aciclovir than the thymidine kinases of the host cell. The action of aciclovir is more effective in virus-infected host cells because the viral thymidine kinase is a more efficient catalyst for the monophosphorylation of aciclovir than the thymidine kinases of the host cell. prof. aza

41. This leads to an increase in the concentration of the aciclovir triphosphate, which has 100-fold greater affinity for viral DNA polymerase than human DNA polymerase. This leads to an increase in the concentration of the aciclovir triphosphate, which has 100-fold greater affinity for viral DNA polymerase than human DNA polymerase. As a result, it preferentially competitively inhibits viral DNA polymerase and so prevents the virus from replicating. As a result, it preferentially competitively inhibits viral DNA polymerase and so prevents the virus from replicating. prof. aza

42. However, resistance has been reported due to changes in the viral mRNA responsible for the production of the viral thymidine kinase. However, resistance has been reported due to changes in the viral mRNA responsible for the production of the viral thymidine kinase. Aciclovir also acts by terminating chain formation. The aciclovir–DNA complex formed by the drug also irreversibly inhibits DNA polymerase. Aciclovir also acts by terminating chain formation. The aciclovir–DNA complex formed by the drug also irreversibly inhibits DNA polymerase. prof. aza

43. Vidarabine Vidarabine is active against herpes simplex and herpes varicella-zoster. Vidarabine is active against herpes simplex and herpes varicella-zoster. However, the drug does give rise to nausea, vomiting, tremors, dizziness and seizures. In addition it has been reported to be mutagenic, teratogenic and carcinogenic in animal studies. However, the drug does give rise to nausea, vomiting, tremors, dizziness and seizures. In addition it has been reported to be mutagenic, teratogenic and carcinogenic in animal studies. prof. aza

44. Vidarabine is administered by intravenous infusion and topical application. It has a half-life of about one hour, the drug being rapidly deaminated to arabinofuranosyl hypoxanthine (ara-HX) by adenosine deaminase. Vidarabine is administered by intravenous infusion and topical application. It has a half-life of about one hour, the drug being rapidly deaminated to arabinofuranosyl hypoxanthine (ara-HX) by adenosine deaminase. prof. aza

45. This enzyme is found in the serum and red blood cells. Ara-HX, which also exhibits a weak antiviral action, has a half-life of about 3.5 hours. This enzyme is found in the serum and red blood cells. Ara-HX, which also exhibits a weak antiviral action, has a half-life of about 3.5 hours. prof. aza

47. Zidovudine (AZT) Zidovudine was originally synthesised in 1964 as an analogue of thymine by J. Horwitz as a potential antileukaemia drug. Zidovudine was originally synthesised in 1964 as an analogue of thymine by J. Horwitz as a potential antileukaemia drug. It was found to be unsuitable for use in this role and for 20 years was ignored, even though in 1974 W. Osterag et al. reported that it was active against Friend leukaemia virus, a retrovirus. It was found to be unsuitable for use in this role and for 20 years was ignored, even though in 1974 W. Osterag et al. reported that it was active against Friend leukaemia virus, a retrovirus. prof. aza

48. However, the identification in 1983 of the retrovirus HIVas the source of AIDS resulted in the virologist M. St Clair setting up a screening programme for drugs that could attack HIV However, the identification in 1983 of the retrovirus HIVas the source of AIDS resulted in the virologist M. St Clair setting up a screening programme for drugs that could attack HIV prof. aza

49. Fourteen compounds were selected and screened against Friend leukaemia virus and a second retrovirus called Harvey sarcoma virus. Fourteen compounds were selected and screened against Friend leukaemia virus and a second retrovirus called Harvey sarcoma virus. This screen led to the discovery of zidovudine (AZT), which was rapidly developed into clinical use on selected patients in 1986. This screen led to the discovery of zidovudine (AZT), which was rapidly developed into clinical use on selected patients in 1986. prof. aza

51. AZT is converted by the action of cellular thymidine kinase to the 5- triphosphate. AZT is converted by the action of cellular thymidine kinase to the 5- triphosphate. This inhibits the enzyme reverse transcriptase in the retrovirus, which effectively prevents it from forming the viral DNA necessary for viral replication. This inhibits the enzyme reverse transcriptase in the retrovirus, which effectively prevents it from forming the viral DNA necessary for viral replication. prof. aza

52. The incorporation of AZT into the nucleic acid chain also results in chain termination because the presence of the 3-azide group prevents the reaction of the chain with the 5-triphosphate of the next nucleotide waiting to join the chain (Fig. 10.45). The incorporation of AZT into the nucleic acid chain also results in chain termination because the presence of the 3-azide group prevents the reaction of the chain with the 5-triphosphate of the next nucleotide waiting to join the chain (Fig. 10.45). prof. aza

53. AZT is also active against mammalian DNA polymerase and although its affinity for this enzyme is about 100-fold less this action is thought to be the cause of some of its unwanted side effects. AZT is also active against mammalian DNA polymerase and although its affinity for this enzyme is about 100-fold less this action is thought to be the cause of some of its unwanted side effects. prof. aza

54. Zidovudine is active against the retroviruses (see section 10.14.2) that cause AIDS (HIV virus) and certain types of leukaemia. Zidovudine is active against the retroviruses (see section 10.14.2) that cause AIDS (HIV virus) and certain types of leukaemia. It also inhibits cellular a-DNA polymerase but only at concentrations in excess of 100-fold greater than those needed to treat the viral infection. It also inhibits cellular a-DNA polymerase but only at concentrations in excess of 100-fold greater than those needed to treat the viral infection. prof. aza

55. The drug may be administered orally or by intravenous infusion. The bioavailability from oral administration is good, the drug being distributed into most body fluids and tissues. The drug may be administered orally or by intravenous infusion. The bioavailability from oral administration is good, the drug being distributed into most body fluids and tissues. However, when used to treat AIDS it has given rise to gastrointestinal disorders, skin rashes, insomnia, anaemia, fever, headaches, depression and other unwanted effects. However, when used to treat AIDS it has given rise to gastrointestinal disorders, skin rashes, insomnia, anaemia, fever, headaches, depression and other unwanted effects. prof. aza

56. Resistance Resistance increases with time. This is known to be due to the virus developing mutations’ which result in changes in the amino acid sequences in the reverse transcriptase. Resistance increases with time. This is known to be due to the virus developing mutations’ which result in changes in the amino acid sequences in the reverse transcriptase. prof. aza

57. Didanosine Didanosine is used to treat some AZT- resistant strains of HIV. It is also used in combination with AZT to treat HIV. Didanosine is administered orally in dosage forms that contain antacid buffers to prevent conversion by the stomach acids to hypoxanthine Didanosine is used to treat some AZT- resistant strains of HIV. It is also used in combination with AZT to treat HIV. Didanosine is administered orally in dosage forms that contain antacid buffers to prevent conversion by the stomach acids to hypoxanthine prof. aza

58. However, in spite of the use of buffers the bioavailability from oral administration is low. However, in spite of the use of buffers the bioavailability from oral administration is low. The drug can cause nausea, abdominal pain and peripheral neuropathy, amongst other symptoms. Drug resistance occurs after prolonged use. The drug can cause nausea, abdominal pain and peripheral neuropathy, amongst other symptoms. Drug resistance occurs after prolonged use. prof. aza

60. Didanosine is converted by viral and cellular kinases to the monophosphate and then to the triphosphate. Didanosine is converted by viral and cellular kinases to the monophosphate and then to the triphosphate. In this form it inhibits reverse transcriptase and in addition its incorporation into the DNA chain terminates the chain because the drug has no 3-hydroxy group (Fig. 10.45). In this form it inhibits reverse transcriptase and in addition its incorporation into the DNA chain terminates the chain because the drug has no 3-hydroxy group (Fig. 10.45). prof. aza

61. Host cell penetration inhibitors The principal drugs that act in this manner are amantadine and rimantadine (Fig. 10.46). The principal drugs that act in this manner are amantadine and rimantadine (Fig. 10.46). Both amantadine and rimantadine are also used to treat Parkinson’s disease. However, their mode of action in this disease is different from their action as antiviral agents. Both amantadine and rimantadine are also used to treat Parkinson’s disease. However, their mode of action in this disease is different from their action as antiviral agents. prof. aza

63. Amantadine hydrochloride Amantadine hydrochloride is effective against influenza A virus but is not effective against the influenza B virus. When used as a prophylactic, it is believed to give up to 80 per cent protection against influenza A virus infections Amantadine hydrochloride is effective against influenza A virus but is not effective against the influenza B virus. When used as a prophylactic, it is believed to give up to 80 per cent protection against influenza A virus infections prof. aza

65. The drug acts by blocking an ion channel in the virus membrane formed by the viral protein M2. This is believed to inhibit the disassembly of the core of the virion and its penetration of the host (see section 10.14.1). The drug acts by blocking an ion channel in the virus membrane formed by the viral protein M2. This is believed to inhibit the disassembly of the core of the virion and its penetration of the host (see section 10.14.1). prof. aza

66. Amantadine hydrochloride has a good bioavailability on oral administration, being readily absorbed and distributed to most body fluids and tissues. Amantadine hydrochloride has a good bioavailability on oral administration, being readily absorbed and distributed to most body fluids and tissues. Its elimination time is 12–18 hours. However, its use can result in depression, dizziness, insomnia and gastrointestinal disturbances, amongst other unwanted side effects. Its elimination time is 12–18 hours. However, its use can result in depression, dizziness, insomnia and gastrointestinal disturbances, amongst other unwanted side effects. prof. aza

67. Rimantadine hydrochloride Rimantadine hydrochloride is an analogue of amantadine hydrochloride. Rimantadine hydrochloride is an analogue of amantadine hydrochloride. It is more effective against influenza A virus than amantadine. Its mode of action is probably similar to that of amantadine. It is more effective against influenza A virus than amantadine. Its mode of action is probably similar to that of amantadine. prof. aza

68. The drug is readily absorbed when administered orally but undergoes extensive first-pass metabolism. However, in spite of this, its elimination half-life is double that of amantadine. Furthermore, CNS side effects are significantly reduced. The drug is readily absorbed when administered orally but undergoes extensive first-pass metabolism. However, in spite of this, its elimination half-life is double that of amantadine. Furthermore, CNS side effects are significantly reduced. prof. aza

69. Inhibitors of viral protein synthesis The principal compounds that act as inhibitors of protein synthesis are the interferons. The principal compounds that act as inhibitors of protein synthesis are the interferons. These compounds are members of a naturally occurring family of glycoprotein hormones (RMM 20 000– 160 000), which are produced by nearly all types of eukaryotic cell. These compounds are members of a naturally occurring family of glycoprotein hormones (RMM 20 000– 160 000), which are produced by nearly all types of eukaryotic cell. prof. aza

70. Three general classes of interferons are known to occur naturally in mammals, namely: the α-interferons produced by leucocytes, β-interferons produced by fibroblasts and γ- interferons produced by T lymphocytes. At least twenty α-, two β- and two γ- interferons have been identified Three general classes of interferons are known to occur naturally in mammals, namely: the α-interferons produced by leucocytes, β-interferons produced by fibroblasts and γ- interferons produced by T lymphocytes. At least twenty α-, two β- and two γ- interferons have been identified prof. aza

71. Interferons form part of the human immune system. It is believed that the presence of virions, bacteria and other antigens in the body switches on the mRNA that controls the production and release of interferon. Interferons form part of the human immune system. It is believed that the presence of virions, bacteria and other antigens in the body switches on the mRNA that controls the production and release of interferon. This release stimulates other cells to produce and release more interferon. This release stimulates other cells to produce and release more interferon. prof. aza

72. Interferons are thought to act by initiating the production in the cell of proteins that protect the cells from viral attack. Interferons are thought to act by initiating the production in the cell of proteins that protect the cells from viral attack. The main action of these proteins takes the form of inhibiting the synthesis of viral mRNA and viral protein synthesis. The main action of these proteins takes the form of inhibiting the synthesis of viral mRNA and viral protein synthesis. prof. aza

73. a- Interferons also enhance the activity of killer T cells associated with the immune system. (see section 14.5.5). a- Interferons also enhance the activity of killer T cells associated with the immune system. (see section 14.5.5). prof. aza

74. The main action of these proteins takes the form of inhibiting the synthesis of viral mRNA and viral protein synthesis. The main action of these proteins takes the form of inhibiting the synthesis of viral mRNA and viral protein synthesis. α- Interferons also enhance the activity of killer T cells associated with the immune system. α- Interferons also enhance the activity of killer T cells associated with the immune system. prof. aza

75. A number of a-interferons have been manufactured and proven to be reasonably effective against a number of viruses and cancers. A number of a-interferons have been manufactured and proven to be reasonably effective against a number of viruses and cancers. Interferons are usually given by intravenous, intramuscular or subcutaneous injection. Interferons are usually given by intravenous, intramuscular or subcutaneous injection. prof. aza

76. However, their administration can cause adverse effects, such as headaches, fevers and bone marrow depression, that are dose related. However, their administration can cause adverse effects, such as headaches, fevers and bone marrow depression, that are dose related. The formation and release of interferon by viral and other pathological stimulation has resulted in a search for chemical inducers of endogenous interferon. The formation and release of interferon by viral and other pathological stimulation has resulted in a search for chemical inducers of endogenous interferon. prof. aza

77. Administration of a wide range of compounds has resulted in the induction of interferon production. However, no clinically useful compounds have been found for humans’ although tilorone is effective in inducing interferon in mice. Administration of a wide range of compounds has resulted in the induction of interferon production. However, no clinically useful compounds have been found for humans’ although tilorone is effective in inducing interferon in mice. prof. aza