The document discusses various antiviral drugs, their mechanisms of action, and their uses. It describes nucleoside reverse transcriptase inhibitors (NRTI) like zidovudine, didanosine, zalcitabine, and lamivudine which work by competing for incorporation into viral DNA and terminating the chain. It also discusses protease inhibitors like saquinavir, indinavir, and ritonavir which prevent viral replication by binding to viral proteases and blocking protein cleavage. Finally, it mentions other antivirals like amantadine, rimantadine, acyclovir, and gancyclovir which interfere with viral attachment, uncoating, or nucleic acid replication
1. Ms. Mandakini Sampat Holkar
Assistant Professor
Dept. of Pharmaceutics
Shri Vithal Education and Research
Institute’s College of Pharmacy,
Pandharpur
4. Introduction
Antivirals are a class of medications that are used to treat
viral infections These drugs act by arresting the viral
replication cycle at various stages. Most of the antiviral
drugs currently available are used to treat infections caused
by HIV, herpes viruses, hepatitis B and C viruses, and
influenza A and B viruses. Because viruses are obligate,
intracellular parasites, it is difficult to find drug targets that
interfere with viral replication without harming the host
cells.
5. Viral replication cycle Target Antiviral drug
Fusion with host cell •Attachment maraviroc*
•Penetration •Fusion inhibitor (e.g.,
enfuvirtide)*
Uncoating •Release of nucleic acid •Amantadine
Replication of viral
genome
•Reverse transcription •NRTI (e.g., lamivudine)*
•NNRTI (e.g., nevirapine,)*
•DNA integration (integrase) •Integrase inhibitors (e.g.,
dolutegravir, elvitegravir,
raltegravir)*
•Nucleic acid synthesis (DNA
polymerase)
•Guanosine analogs (e.g.,
acyclovir ganciclovir)
•Guanine nucleotide synthesis
inhibitor: ribavirin
Protein synthesis and
assembly of viral
components
•Protein synthesis
(transcription and translation)
•Interferon alpha
Release of new viruses
from host cell
•Viral budding •Neuraminidase inhibitors (e.g.,
oseltamivir, zanamivir)
6. Classification
1. Anti-herpes virus: Idoxuridine, acyclovir, valacyclovir,
famciclovir, ganciclovir, forscarnet
Except forscarnet which is an inhibitor of DNA polymerase and
reverse transcriptase, others are purine and pyrimidine anlaogues.
2. Anti-retrovirus:
a. Nucleoside reverse transcriptase inhibitors (NRTIs): Zidovudine
(AZT), Didanosine, Zalcitabine, Stavudine, Lamivudine, Abacavir
b. Non-nucleoside reverse transcriptase inhibitors
(NNRTIs):Nevirapine, Efavirenz, Delaviridine
c. Protease inhibitors: Ritonavir, Indinavir, Nelfinavir, Saquinavir,
Lopinavir
3. Anti-influenza virus: Amatidine, Rimantadine
4. Nonselective antiviral drugs: Ribavirin, Lamivudine, Interferon
alpha
9. Rimantadine
Rimantadine (INN, sold under the trade name Flumadine) is
an orally administered antiviral drug used to treat, and in rare
cases prevent, influenzavirus A infection. When taken within
one to two days of developing symptoms, rimantadine can
shorten the duration and moderate the severity of influenza.
11. Aciclovir
Aciclovir (ACV), also known as acyclovir, is an
antiviral medication.
Aciclovir is a nucleoside analogue that mimics
guanosine.It works by decreasing the production of the
virus's DNA.
13. Aciclovir is used for the treatment of
herpes simplex virus (HSV) and varicella zoster virus infections,
including:
Genital herpes simplex (treatment and prevention)
Neonatal herpes simplex
Herpes simplex labialis (cold sores)
Shingles
Acute chickenpox in immunocompromised patients
Herpes simplex encephalitis
Acute mucocutaneous HSV infections in immunocompromised
patients
Herpes of the eye and herpes simplex blepharitis (a chronic
(long-term) form of herpes eye infection)
Prevention of herpes viruses in immunocompromised people
(such as people undergoing cancer chemotherapy)
USES
14. Gancyclovir
Ganciclovir triphosphate is a competitive inhibitor of
deoxyguanosine triphosphate (dGTP) incorporation into DNA
and preferentially inhibits viral DNA polymerases more than
cellular DNA polymerases. In addition, ganciclovir
triphosphate serves as a poor substrate for chain elongation,
thereby disrupting viral DNA synthesis by a second route
Ganciclovir is an antiviral medication used to treat
cytomegalovirus (CMV) infections.
15. Idoxuridine trifluoride
Idoxuridine is an anti-herpesvirus antiviral drug.
It is a nucleoside analogue, a modified form of deoxyuridine,
similar enough to be incorporated into viral DNA replication,
Idoxuridine is mainly used topically to treat herpes simplex
keratitis. Epithelial lesions, especially initial attacks
presenting with a dendritic ulcer, are most responsive to
therapy, while infection with stromal involvement are less
responsive.Idoxuridine is ineffective against herpes simplex
virus type 2 and varicella-zoster.
17. Zidovudine
Zidovudine (ZDV), also known as azidothymidine (AZT), is
an antiretroviral medication used to prevent and treat
HIV/AIDS. It is generally recommended for use with other
antiretrovirals. It may be used to prevent mother-to-child
spread during birth or after a needlestick injury or other
potential exposure. It is sold both by itself and together as
lamivudine/zidovudine and abacavir/lamivudine/zidovudine. It
can be used by mouth or by slow injection into a vein
18. Didanosine
Didanosine (ddI, DDI), marketed under the trade names
Videx, is a medication used to treat HIV/AIDS. It is used in
combination with other medications as part of highly active
antiretroviral therapy (HAART). It is of the reverse-
transcriptase inhibitor class.
19. Didanosine (ddI) is a nucleoside analogue of adenosine. It differs from other
nucleoside analogues, because it does not have any of the regular bases, instead it
has hypoxanthine attached to the sugar ring.
Mechanism of action
Didanosine
(ddI)
active metabolite
of
dideoxyadenosine
triphosphate,
ddATP
it acts as a chain
terminator by
incorporation
inhibits viral
reverse
transcriptase by
competing with
natural dATP
Didanosine
phosphorylated
By cellular enzymes
20. Zalcitabine
Zalcitabine (2′-3′-dideoxycytidine, ddC), also called
dideoxycytidine, is a nucleoside analog reverse-transcriptase
inhibitor (NRTI) sold under the trade name Hivid. Zalcitabine was
the third antiretroviral to be approved by the Food and Drug
Administration (FDA) for the treatment of HIV/AIDS. It is used as
part of a combination regimen.
21. Zalcitabine is an analog of pyrimidine. It is a derivative of the naturally existing
deoxycytidine, made by replacing the hydroxyl group in position 3' with a
hydrogen.
Mechanism of action
.
Zalcitabine
(ddc)
active metabolite
of
its active
triphosphate
form, ddCTP
it terminate
chain elongation
due to loss of
OH group
inhibits viral
reverse
transcriptase
Phosphorylated in
T cells
By cellular enzymes
22. Lamivudine
Lamivudine, commonly called 3TC, is an antiretroviral medication
used to prevent and treat HIV/AIDS. It is also used to treat chronic
hepatitis B when other options are not possible. It is effective
against both HIV-1 and HIV-2.It is typically used in combination
with other antiretrovirals such as zidovudine and abacavir
23. Lamivudine is an analogue of cytidine. It can inhibit both types (1 and 2) of
HIV reverse transcriptase and also the reverse transcriptase of hepatitis B virus.
Mechanism of action
Lamivudine
They inhibit the HIV
reverse transcriptase
enzyme competitively
and act as a chain
terminator of DNA
synthesis
that compete for
incorporation into viral
DNA.
active metabolites
The lack of a 3'-OH
group in the
incorporated
nucleoside analogue
prevents the formation
of the 5' to 3'
phosphodiester
linkage essential for
DNA chain elongation
viral DNA growth is
terminated.
24. Protease inhibitors (PIs) are a class of antiviral drugs that are
widely used to treat HIV/AIDS and hepatitis C. Protease
inhibitors prevent viral replication by selectively binding to
viral proteases (e.g. HIV-1 protease) and blocking proteolytic
cleavage of protein precursors that are necessary for the
production of infectious viral particles
25. Saquinavir
Saquinavir (SQV), sold under the brand names Invirase
and Fortovase, is an antiretroviral drug used together
with other medications to treat or prevent HIV/AIDS
26. Saquinavir is a protease inhibitor. Proteases are enzymes that
cleave protein molecules into smaller fragments. HIV
protease is vital for both viral replication within the cell and
release of mature viral particles from an infected cell.
Saquinavir binds to the active site of the viral protease and
prevents cleavage of viral polyproteins, preventing maturation
of the virus. Saquinavir inhibits both HIV-1 and HIV-2
proteases.
Mechanism of action
27. Indinavir (IDV)
trade name Crixivan, made by Merck) is a protease
inhibitor used as a component of highly active antiretroviral
therapy to treat HIV/AIDS.
28. Ritonavir
Ritonavir (RTV), sold under the trade name Norvir, is an
antiretroviral medication used along with other medications to
treat HIV/AIDS. This combination treatment is known as highly
active antiretroviral therapy (HAART).Often a low dose is used
with other protease inhibitors. It may also be used in combination
with other medications for hepatitis C. It is taken by mouth. The
capsules of the medication do not work the same as the tablets.
