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Types of Antiviral Drugs:
Amantadine is a low molecular weight quantity which is operational along with-door to influenza virus A. It prevents optional accessory as dexterously as un-coating of endocytosed virions. It binds to the viral matrix proteins of influenza virus and thereby prevents the conformational changes required for un-coating. A connected merged Rimantadine has a related effect approaching influenza virus. A number of nucleoside analogues have been used as antiviral drugs. Among these are acyclovir, idoxuridine, ribavirin, vidarabine, trifluridine, azidothymidine etc.
Structures of Acyclovir and Deoxyguanosine
Because of the structural sympathy of acyclovir and deoxyguanosine, the viral enzyme, nucleoside kinase phosphorylates acyclovir to its phosphate forming a traitorous nucleotide which cannot be incorporated into DNA i.e. DNA polymerization is inhibited. Acyclovir derivatives, gone famciclovir and ganciclovir are same in mode of operate .
Inhibition of Viral DNA Synthesis
Acyclovir and its derivatives have been found to be energetic adjoining herpes virus infections, particularly genital herpes. It has after that effect going approximately for chicken pox. Other nucleoside analogues have along with been used as antiviral drugs, taking into consideration idoxuridine (5-iodo-deoxyuridine), trifluridine, vidarabine (adenine arabinoside) etc.
Idoxuridine is a thymidine analogue and is incorporated into viral DNA blocking bonus polymerisation of DNA. Vidarabine has structural empathy once deoxyadenosine and has a associated effect on the subject of viral DNA synthesis as idoxuridine. These drugs are mainly used in infections caused by herpes virus.
Structural Similarity along together in addition to Idoxuridine and Thymidine
An important strategy of inhibiting retroviruses such as HIV is to block the moving picture of reverse transcriptase, the viral enzyme required for synthesis of DNA from the genomic RNA of these viruses. Reverse transcriptase is absent in the host cells. Several chemotherapeutic agents have been developed as potential reverse transcriptase inhibitor, such as zidovudine (azidothymidine, AZT), didanosine and zalcitabine.
These agents inhibit synthesis of DNA from viral RNA by specifically blocking the to-do of reverse transcriptase. They have been found useful in HIV infection causing AIDS. Zidovudine structurally resembles thymidine (Fig. 6.38).
Structure of Zidovudine
Didanosine and zalcitabine are less toxic than zidovudine. These agents exploit as competitive inhibitors of thymidine in the reverse transcription of viral genomic RNA to ds-DNA. As this step is vital for viral replication, these agents can effectively quantity uphill less viral multiplication in AIDS patients.
The mechanism of act appears to be the incorporation of the drug in the elongating DNA chain in area of thymidine, thereby inhibiting bonus count of nucleotide. The presence of the azide action in 3-viewpoint in place of an OH-outfit which is valuable for DNA polymerisation prevents chain elongation. Didanosine (dideoxyinosine) and zalcitabine (dideoxy- cytidine) have a thesame mode of produce an effect.
Another agent which inhibits reverse transcription of retroviruses is foscarnet (phosphonoformic cutting). It inhibits DNA polymerization by binding to the pyrophosphate receptor, in view of that that merger of nucleotides from the precursor nucleoside triphosphates into DNA cannot come clean place. Other reverse transcriptase inhibiting drugs add occurring nevirapine and delaviridine.
Another admittance to act HIV is to inhibit the viral protease which is essential for cleaving polyprotein molecules into fragments that are used for assembly of auxiliary viral particles. The protease inhibitors developed as potential drugs for HIV therapy complement indinavir, saquinavir and ritonavir.
The protease inhibitors are amino bitter analogues and they achievement as competitive inhibitors in the viral protease salutation. As a outcome, the long protein molecules cannot be cleaved to smaller ones required for virion assembly. Thus, assembly of progeny virions is prevented.
One of the best strategies to manage a viral disease would be to prevent the virus from entering the turn host cells. This could be achieved through vaccination which induces restructure of antibodies that would react taking into account the surface proteins of viral particles and would defer their relationships into the host cell. In recent time, antiviral drugs have been synthesized which fighting in a re same habit.
One class of these drugs is the neuraminidase inhibitors which are creature used adjoining influenza virus. The virions of influenza virus contain two types of spikes upon their envelope one type contains haemagglutinin ruckus and the calculation type contains neuraminidase objection.
These spikes receive portion in add-on of influenza virus to the cells of the respiratory tract of the host. Neuraminidase inhibitors, bearing in mind zanamivir and oseltamivir phosphate, block optional connection of influenza virus particles by clogging the sites of the host cell surface where the virions could include.
The concern to the lead of these not well-disposed of-influenza drugs was only possible because the exact knowledge of biochemistry of extra of the virus to the host cell surface was known. This proves that considering strengthening of knowledge of viral infection in difficult, more and more operating antiviral drugs would be discovered. But till now, the most in pursuit behave adjoining viral diseases continues to be vaccination which induces both humoral (through antibodies) and cell-mediated (through killer T-lymphocytes) immunity in the body.
Most vaccines against viral diseases utilize inactivated or attenuated viruses. Such vaccines e.g. the Salk vaccine against poliomyelitis, uses alive viruses inactivated by formaldehyde, or Sabin vaccine, next against the same disease, uses attenuated viruses.
These vaccines have certain amount of risk, though intensely negligible, because the inactivation may not be 100 per cent, or in rare cases attenuated viruses may revert to their indigenous pathogenic form. In more recent years, sub-unit vaccines have been developed by genetic engineering.
For example, hepatitis B viral vaccine has been prepared by transferring the viral gene coding a capsid protein to yeast. The transgenic yeast produces the viral capsid protein which after unfriendliness and purification has been used to prepare the hepatitis B virus vaccine. The vaccine containing the capsid protein induces immunity against hepatitis B infection. These vaccines are sometimes called DNA vaccines, because they change recombinant DNA technology.
Amantadine is a low molecular weight quantity which is operational along with-door to influenza virus A. It prevents optional accessory as dexterously as un-coating of endocytosed virions. It binds to the viral matrix proteins of influenza virus and thereby prevents the conformational changes required for un-coating. A connected merged Rimantadine has a related effect approaching influenza virus. A number of nucleoside analogues have been used as antiviral drugs. Among these are acyclovir, idoxuridine, ribavirin, vidarabine, trifluridine, azidothymidine etc.
Structures of Acyclovir and Deoxyguanosine
Because of the structural sympathy of acyclovir and deoxyguanosine, the viral enzyme, nucleoside kinase phosphorylates acyclovir to its phosphate forming a traitorous nucleotide which cannot be incorporated into DNA i.e. DNA polymerization is inhibited. Acyclovir derivatives, gone famciclovir and ganciclovir are same in mode of operate .
Inhibition of Viral DNA Synthesis
Acyclovir and its derivatives have been found to be energetic adjoining herpes virus infections, particularly genital herpes. It has after that effect going approximately for chicken pox. Other nucleoside analogues have along with been used as antiviral drugs, taking into consideration idoxuridine (5-iodo-deoxyuridine), trifluridine, vidarabine (adenine arabinoside) etc.
Idoxuridine is a thymidine analogue and is incorporated into viral DNA blocking bonus polymerisation of DNA. Vidarabine has structural empathy once deoxyadenosine and has a associated effect on the subject of viral DNA synthesis as idoxuridine. These drugs are mainly used in infections caused by herpes virus.
Structural Similarity along together in addition to Idoxuridine and Thymidine
An important strategy of inhibiting retroviruses such as HIV is to block the moving picture of reverse transcriptase, the viral enzyme required for synthesis of DNA from the genomic RNA of these viruses. Reverse transcriptase is absent in the host cells. Several chemotherapeutic agents have been developed as potential reverse transcriptase inhibitor, such as zidovudine (azidothymidine, AZT), didanosine and zalcitabine.
These agents inhibit synthesis of DNA from viral RNA by specifically blocking the to-do of reverse transcriptase. They have been found useful in HIV infection causing AIDS. Zidovudine structurally resembles thymidine (Fig. 6.38).
Structure of Zidovudine
Didanosine and zalcitabine are less toxic than zidovudine. These agents exploit as competitive inhibitors of thymidine in the reverse transcription of viral genomic RNA to ds-DNA. As this step is vital for viral replication, these agents can effectively quantity uphill less viral multiplication in AIDS patients.
The mechanism of act appears to be the incorporation of the drug in the elongating DNA chain in area of thymidine, thereby inhibiting bonus count of nucleotide. The presence of the azide action in 3-viewpoint in place of an OH-outfit which is valuable for DNA polymerisation prevents chain elongation. Didanosine (dideoxyinosine) and zalcitabine (dideoxy- cytidine) have a thesame mode of produce an effect.
Another agent which inhibits reverse transcription of retroviruses is foscarnet (phosphonoformic cutting). It inhibits DNA polymerization by binding to the pyrophosphate receptor, in view of that that merger of nucleotides from the precursor nucleoside triphosphates into DNA cannot come clean place. Other reverse transcriptase inhibiting drugs add occurring nevirapine and delaviridine.
Another admittance to act HIV is to inhibit the viral protease which is essential for cleaving polyprotein molecules into fragments that are used for assembly of auxiliary viral particles. The protease inhibitors developed as potential drugs for HIV therapy complement indinavir, saquinavir and ritonavir.
The protease inhibitors are amino bitter analogues and they achievement as competitive inhibitors in the viral protease salutation. As a outcome, the long protein molecules cannot be cleaved to smaller ones required for virion assembly. Thus, assembly of progeny virions is prevented.
One of the best strategies to manage a viral disease would be to prevent the virus from entering the turn host cells. This could be achieved through vaccination which induces restructure of antibodies that would react taking into account the surface proteins of viral particles and would defer their relationships into the host cell. In recent time, antiviral drugs have been synthesized which fighting in a re same habit.
One class of these drugs is the neuraminidase inhibitors which are creature used adjoining influenza virus. The virions of influenza virus contain two types of spikes upon their envelope one type contains haemagglutinin ruckus and the calculation type contains neuraminidase objection.
These spikes receive portion in add-on of influenza virus to the cells of the respiratory tract of the host. Neuraminidase inhibitors, bearing in mind zanamivir and oseltamivir phosphate, block optional connection of influenza virus particles by clogging the sites of the host cell surface where the virions could include.
The concern to the lead of these not well-disposed of-influenza drugs was only possible because the exact knowledge of biochemistry of extra of the virus to the host cell surface was known. This proves that considering strengthening of knowledge of viral infection in difficult, more and more operating antiviral drugs would be discovered. But till now, the most in pursuit behave adjoining viral diseases continues to be vaccination which induces both humoral (through antibodies) and cell-mediated (through killer T-lymphocytes) immunity in the body.
Most vaccines against viral diseases utilize inactivated or attenuated viruses. Such vaccines e.g. the Salk vaccine against poliomyelitis, uses alive viruses inactivated by formaldehyde, or Sabin vaccine, next against the same disease, uses attenuated viruses.
These vaccines have certain amount of risk, though intensely negligible, because the inactivation may not be 100 per cent, or in rare cases attenuated viruses may revert to their indigenous pathogenic form. In more recent years, sub-unit vaccines have been developed by genetic engineering.
For example, hepatitis B viral vaccine has been prepared by transferring the viral gene coding a capsid protein to yeast. The transgenic yeast produces the viral capsid protein which after unfriendliness and purification has been used to prepare the hepatitis B virus vaccine. The vaccine containing the capsid protein induces immunity against hepatitis B infection. These vaccines are sometimes called DNA vaccines, because they change recombinant DNA technology.
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