antiviral drugs mechanism of action
The virus does not take only nutrition from the host cell but
also a synthesise a new particle through metabolic machinery. The viral
chemotherapy is very difficult it should be required interference with their
cellular metabolism in the host cell. that’s why here, further discuss the antiviral
drugs mechanism of action in details.
In the antiviral drugs mechanism of action various classes
drugs have their own mechanism of action. In antiviral drugs 4 major class.
- Antiherpes agents
- Antiretroviral agents
- Anti-influenza drugs
- Other antiviral drugs
1. antiheres agents:
[acyclovir, fancyclovir,
vancyclovir, penciclovir, ganciclovir, foscarnet, idoxuridine]
In antiviral drugs mechanism of action, All antiherpes
agents are act against the herpetic infection. Most common drugs used as antiherpes agents are
·
Acyclovir, vancyclovir, penciclovir,
famciclovir, ganciclovir
·
Idoxuridine & foscarnet.
ACYCLOVIR: (antiviral drugs mechanism of action)
In antiviral drugs mechanism of action, acyclovir is purine
nucleotide analogues that act as an antiherpes activity.
Acyclovir is most effective against this type of herpes
infection,
HSV -1: herpes labialis, herpes encephalitis, herpes
oesophagitis
HSV -2: genital herpes
VZV (varicella-zoster virus): herpes zoster, chicken
pox.
HSV thymidine kinase acts on the acyclovir and produces acyclovir
monophosphate ➞a further cellular enzyme acts on the acyclovir monophosphate and produce acyclovir
diphosphate➞ than
further acyclovir diphosphate are converted into acyclovir triphosphate
with the help of a cellular enzyme.
Than acyclovir triphosphate is inhibiting viral
replication and also inhibit viral synthesis. So, the triphosphate
derivatives are also a inhibit synthesis of viral DNA. And inhibit viral
replication.
Acyclovir is highly potent drugs. the therapeutic index of
acyclovir is high and produces low toxicity.
Use and adverse effect of acyclovir:
Acyclovir is administered by oral, i.v and topical
administration. But its oral
bioavailability is very less. Its also used in different types of herpes
infection & produce some common GI side effect but in a high dose that produces
the tremor, nephrotoxicity, convulsion & etc.
VANCYCLOVIR (antiviral drugs mechanism of action)
It’s a prodrug of the acyclovir (ester prodrug).
In intestine and liver, vancyclovir are completely converted
in acyclovir ➞ to intracellular activation acyclovir is converted in acyclovir triphosphate ➞ it’s affect the HSV 1 & 2, VZV & hepatitis B virus. ® inhibit the DNA synthesis
and also inhibit viral replication.
Use and adverse effect of vancyclovir:
Vancyclovir is used in genital herpes, herpes zoster,
orolabial herpes. The adverse effect of vancyclovir is nausea, vomiting and some
skin rashes. In a high dose of acyclovir, some CNS symptoms are produced.
FNACYCLOVIR (antiviral drugs mechanism of action)
It’s a prodrug of the penciclovir (ester prodrug)
fancyclovir is converted to penciclovir ➞ to also a pencylovir are
converted to penciclovir triphosphate ➞ that’s same as a vancyclovir inhibit the HSV 1 & 2, VZV and hepatitis B
virus DNA synthesis ➞ so, inhibit the DNA replication of the virus.
Use and adverse effect of fancyclovir:
It's used as an alternative of the acyclovir for orolabial
herpes, genital herpes & herpes zoster. Early treatment of the herpes
zoster that reduces the duration of post hepatic neuralgia. Some common side
effect of fancyclovir are vomiting, diarrhoea, nausea & headache.
IDOXURIDINE (antiviral drugs mechanism of action)
Idoxuridine is 5 – iodo – 2 – deoxyuridine (IURD).
Idoxuridine is first pyrimidine antimetabolite that used in antiviral agents.
Idoxuridine work as a thymidine analogues. It's
incorporate with DNA. So, the faulty DNA are breakdown easily. It's effective
against the DNA virus. Its inhibit the DNA synthesis. that’s why viral
replication is also a decrease.
Use and adverse effect of idoxuridine:
Idoxuridine eye drops are very effective than acyclovir eye
ointment. It's also topically used in HSV keratoconjunctivitis. Some side effect
produces like, irritation, itching, swelling and pain. Idoxuridine use is
restricted to superficial dendritic keratitis when its rapid action is
required. With idoxuridine eye drops ocular irritation produce.
2 antiretroviral agents:
In antiviral drugs mechanism of action, antiretroviral is a
most important agents to understand its mechanism of action because they used
in the treatment of AIDS.
Anti retrovirus is acted against the human immune deficiency
virus (HIV virus). These agents are useful in acquired immunodeficiency syndrome
or ARC (aids-related complex).
Various classes of antiretroviral drugs are,
- Nucleotide reverse transcriptase inhibitor
- Non – nucleotide reverse transcriptase inhibitor
- Protease inhibitor
- Fusion inhibitor
- Integrase inhibitor
Nucleoside reverse transcriptase inhibitors, protease
inhibitor and integrase inhibitor are used in infection of HIV 1 and HIV 2.
Where, non- nucleotide reverse transcriptase inhibitor is used in HIV – 1
infection.
(a) nonnucleotide reverse transcriptase
inhibitors: (antiviral drugs mechanism of action)
[zidovudine, stavudine, didanosine, lamivudine, zalcitabine,
abacavir, tenofovir]
These drugs are entering the HIV – infected cells → they are
converted to active triphosphate from cellular kinase → competitively
they inhibit the HIV reverse transcriptase → they are also
incorporate to growing viral DNA. → and in the last termination of DNA chain
elongation.
Here, first, understand the life cycle of HIV. Then understand how all
drugs affect the HIV cycle.
HIV LIFE CYCLE: (a most important part of antiretroviral agent)
First of all entry or fusion
inhibitor in the cell membrane → after entering the cell membrane uncoating
the viral RNA. → with the help of the reverse transcriptase single-strand, viral RNA is converted to double-strand proviral DNA. →
this double-strand DNA virus is integrated with the host DNA cell. →
with the help of transcription, it converts the viral mRNA. → viral mRNA is produced by viral proteins with the help of the translation process.
After that, HIV protease enzyme is
release and maturation of the host cell and host cell are converted to HIV
cell. once it’s converted it doesn’t cure but here, all drugs are used to
prevent the HIV virus infection.
ZIDOVUDINE:
In the antiviral drugs mechanism of action zidovudine is
prototype drugs of nucleotide reverse transcriptase inhibitors. Zidovudine is thymidine
analogues. It’s a first antiretroviral drug used in HIV infection.
It's effective against HIV 1 and HIV 2.
It’s not a cure an HIV infected cell but also a prevent its
uninfected cell.
Understand a zidovudine mechanism first keep in mind HIV life
cycle. Zidovudine triphosphate inhibits the reverse transcriptase.
So, inhibit the double-strand DNA viral.
Also, it inhibits the integrase inhibitor and final stages that do
prevent the cell maturation and release. Zidovudine are prevented the infection
of the new cell. but in proviral that no any effect produces. Because proviral
DNA is already integrated into the host cell.
Zidovudine is effective in orally, well absorbed from the GI
tract. Its metabolise by the glucuronide conjugation and also excreted in the
urine.
Use and side effect if zidovudine:
Combination of other antiretroviral drugs zidovudine are used in
HIV infection. Zidovudine is preventing the vertical transmission of HIV. Also
used in post-exposure prophylaxis.
Many common side effect like bone marrow suppression, neuropaenia
and anaemia are produced. Also, nausea, vomiting, headache, abdominal
discomfort, insomnia What Is Insomnia - Meaning, Symptoms, Treatment, Medication
are produce. In long term therapy, it causes a myopathy, hepatotoxicity, fatigue
and lactic acidosis.
STAVUDINE, DIDANOSINE, ZLCITABINE, LAMIVUDINE, ABACAVIR, EMTRICITABINE
In antiviral drugs mechanism of action, this all drugs has the same
mechanism of action.
This all drugs have transported into the cells and activated to its
respective triphosphate forms ® that inhibit
the HIV reverse transcriptase ® so, don’t
integrated with the host cell ® not produce the viral protein ® finally DNA chain is terminated.
They all are effective in orally. In this drugs lamivudine are
commonly used in antiretroviral therapy because of low toxicity and low efficacy.
Also, emtricitabine are least toxic antiretroviral drugs.
Stavudine with didanosine are combined are not safe because
increase the risk of pancreatic, lactic acidosis and peripheral neuritis.
Abacavir is also produced some side effect like,
hypersensitivity reaction.
(b) Non – nucleotide reverse transcriptase
inhibitors: (antiviral drugs mechanism of action)
[nevirapine, delvirapine, tenofovir]
Non – nucleotide reverse transcriptase inhibitors are highly active
against HIV – 1 virus but it's not any effect produce on HIV – 2 infection. Its
directly inhibit the reverse transcriptase enzyme. So, they finally terminate
the DNA chain.
They do not produce any cross-resistance with nucleotide
reverse transcriptase inhibitors. Also the combination of both drugs (NNRTIs and
NRTIs) is used in the treatment of AIDS.
Some adverse effect produces like GI effect (nausea, vomiting),
skin rashes and CNS disturbance (headache, confusion, bad dream, insomnia.
NEVIRAPINE, EFAVIRENZ, DELAVIRIDINE:
In antiviral drugs mechanism of action, this all drugs are directly bound to the reverse transcriptase enzyme and also a inhibit their
function. So, no any integrated with the host cell and finally terminated the
maturation of cell.
Nevirapine is completely absorbed by the GI tract. Also
a cross the blood-brain barrier and placenta. Nevirapine is also secreted in
breast milk. Metabolise in the liver and excreted through urine.
The common side effect Is skin rashes and also a sometimes,
hepatotoxicity are produced.
efavirenz is administered once daily and has a long
duration of action. Some side effect
produces like skin rashes and CNS side effect.
(c) Protease inhibitors : (antiviral
drugs mechanism of action)
[saquinavir, ritonavir, indinavir, neflinvir, lopinavir]
all the protease inhibitors are the same mechanism of action
produce like this,
All the protease inhibitors inhibit the HIV protease enzyme.
Due to this enzyme are inhibited prevent the cleavage of the viral polypeptide ® final functioning of HIV cell cycle are terminated. ®
Produce an immature or non –
infection viral cell. that is no further effect produce.
Protein inhibitor is given
orally with reverse transcriptase inhibitors. Metabolise in the liver. Some common
side effect produces like, nausea, vomiting and diarrhoea. Also produce
lipodystrophy, insulin resistance, diabetes, skeletal muscle wasting.
Indinavir are specially produce some side effect like hyperbilirubinaemia and nephrolithiasis. Also, a good hydration can be reduced
the incidence of the nephrolithiasis.
Ritonavir inhibits the cytochrome P 450. It's used in both HIV
1 and HIV 2 infection because it inhibits both proteases.
That is used with other
protease inhibitors it can boost the protease inhibitor regimen. Its increase
the bioavailability and half-life of other drugs. Nelfinavir are not combined with
ritonavir.
(d) Fusion
inhibitors (antiviral drugs mechanism
of action)
[efvuridine, maraviroc]
EFVURIDINE:
It is prevent the entry of
HIV 1 membrane with the host cell membrane. In starting block the viral
entry into a host cell. so, no produce any further step preventing because
starting entry is blocked.
Efvuridine is administered through subcutaneously. Its doesn’t exhibit cross-resistance with other
reverse transcriptase and protease inhibitors. In infection site, some common
side effect produces like pain and erythema.
MRAVIROC:
It is a CCR 5 chemokine
antagonist that inhibits the CCR 5 topic strain to host HIV cell. it is given
orally. Some Adverse effect produces like, malaria, cough, arthralgia,
diarrhoea and hepatotoxicity.
(e) Integrate
inhibitors:
[raltegravin]
RALTEGRAVIN:
Raltegravir are also a
inhibit the integrase enzyme. ® That block the
integration of the viral DNA with the host DNA. Raltegravir are generally well
tolerated. Also, some minor side effect produces like, nausea, headache
& fatigue. Raltegravir are also effective against both HIV 1 and HIV 2.
3. anti-influenza drugs:
[amantadine, rimantadine,
zanamivir, oseltamivir]
In antiviral drugs mechanism, fo action anti-influenza agents are useful in the treatment of viral infection.
AMANTADINE: (mechanism of action)
That is a unique tricyclic
amine. Its also produce anti – parkinsonism effect. Its inhibit the
influenza A virus replication. But, in influenza B that is not affected ® The antiviral activity of amantadine is strain-specific.
Its act on both early and
late stages like uncoating stage or viral assembly in viral replication ® Both stages its effective. Thus finally they prevent
the viral replication.
amantadine is well absorbed in GI tract and excreted unchanged in the urine.
Use and side effect of
amantadine:
Amantadine is also used for
parkinsonism & prophylaxis. used in the treatment of influenza A virus
infection. Some common side effect produces like, nausea, headache,
epigastric discomfort, insomnia, confusion, hallucinogen and hypotension.
Amantadine is
contraindicated in pregnancy due to the teratogenic effect.
RIMANTADINE: (mechanism of action)
Rimantidine is methyl
derivatives of amantadine. It is more potent and longer acting. Rimantadine is
better tolerated than parent drugs. the mechanism of action is similar to the
amantadine. It's also a well absorbed in the GI tract and metabolized in liver and
excreted in urine.
OSEITAMIVIR: (mechanism of action)
Oseltamivir are inhibit the
influenza A and B virus. That also an interfering with the release of
virus from the infected cell. used in prevention of influenza virus.
(bird flu and swine flu). Some adverse effect produces nausea, vomiting
and abdominal discomfort.
ZANAMIVIR: (mechanism of action)
In antiviral drugs
mechanism of action, zanamivir drugs mechanism of action is similar to the
oseltamivir. Its administered through inhalation. The oral bioavailability of
zanamivir is low. Some adverse effect produces like dizziness, bronchospasm and
headache. Should not prescribe Airway disease patients.
3. other antiviral agents:
[interferons, ribavirin]
INTERFERONS:
IN other antiviral drugs mechanism of action interferon are
most important. Its produce by the infected cell through recombinant DNA
technology. Mostly three types of interferons like a, β and γ. This three types of interferons are produced an antiviral activity.
Interferons are bind to the specific cell surface receptor and
also affect its viral replication, synthesis of viral mRNA. Interferons are inhibiting the translation and transcription of the cell. it inhibits the many
RNA and DNA virus. But, only INFa2A and INFa2B are available
for clinical used. They produce by the recombinant DNA technology. This is administered
through i.m or s.c.
Use and adverse effect of interferon:
Interferon a
are used for the treatment of hepatic infection in the immunosuppression, also used in venereal warts. It is used in hepatitis B and C.
Interferons are also used in follicular lymphoma, cutaneous
T- cell lymphoma, myeloid leukaemia and multiple myeloma.
Interferons produce some common side effect like fatigue,
aches, fever, dizziness, anorexia, nausea and visual disturbance. Its produce a
neurotoxicity and myelosuppression. Interferon are produced some other side
effect like hypothyroidism, hyperthyroidism, hypotension, alopecia and some
liver dysfunction.
RIBAVIRIN: (mechanism of action)
In antiviral drugs mechanism of action, ribavirin is a purine
nucleotide analogue. It's effective against influenza A & B and other DNA &
double-stranded RNA viruses. Ribavirin monophosphate is inhibited the
cellular enzyme.
That cellular enzyme needed for synthesis of nucleic acid and guanosine
triphosphate (GTP). Ribavirin triphosphate inhibits the viral mRNA synthesis.
Ribavirin is administered in orally or i.v route. its
metabolize in liver and excreted in urine.
Use and adverse effect of ribavirin:
It's effective against the infection of DNA and RNA. Ribavirin
used in Treatment of parainfluenza, influenza, measles, adenovirus. Oral ribavirin
is used in the treatment of chronic hepatitis C infection.
Some common side effect produces like, irritation, cough, nausea,
tiredness, anaemia and insomnia. Also, respiratory irritation and conjunctival
irritation produce. It produces a teratogenic, mutagenic and gonadotoxic toxic effect.
So, not given in during pregnancy.
In antiviral drugs mechanism of action, a various different mechanism
through drugs inhibits the viral infection. Its majorly 4 class of drugs
here, discuss. I hope you will be like these articles. If you like this, comment
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antiviral drugs, mechanism of action of antiviral drugs
