WHAT IS VIRUS?WHAT IS VIRUS?
An obligate intracellular microorganism which
multiply in the nucleus or cytoplasm of host
cell and use metabolic machinery of host cell
is called virus.
The drugs used against the replication of virus
in host cell is known as antiviral drugs.
CLASSIFICATION OF VIRUSCLASSIFICATION OF VIRUS
Viruses are not usually classified into
conventional taxonomic groups but are
usually grouped according to such
properties as size, the type of nucleic acid
they contain, the structure of the capsid
and the number of protein subunits in it,
host species, and immunological
Two classification systems exist:Two classification systems exist:
The Hierarchical virus classification
The Baltimore Classification System
The Hierarchical virus classificationThe Hierarchical virus classification
In 1962 Lwoff, R. W. Horne, and P. Tournier
advanced a comprehensive scheme for the
classification of all viruses consisting of
phylum - class - order - family - subfamily -
genus - species - strain/type.
Four main characteristics are used:
Nature of the nucleic acid: RNA or DNA
Symmetry of the capsid
Presence or absence of an envelopePresence or absence of an envelope
Dimensions of the virion and capsidDimensions of the virion and capsid
All Families have the suffix -viridae e.g.
Caliciviridae, Picornaviridae, Reoviridae.
Genera have the suffix -virus. Within the
Picornaviridae there are 5 genera:
enterovirus, cardiovirus, rhinovirus,
apthovirus and hepatovirus.
The Baltimore ClassificationThe Baltimore Classification
The Baltimore system of virus classification
provides a useful guide with regard to the
various mechanisms of viral genome
These various types of virus genomes can be
broken down into seven fundamentally
different groups, which obviously require
different basic strategies for their replication..
David Baltimore, who originated the scheme,
has given his name to the so-called "Baltimore
Classification" of virus genomes. The
replication strategy of the virus depends on the
nature of its genome. Viruses can be classified
into seven (arbitrary) groups::
I: Double-stranded DNAI: Double-stranded DNA
Some replicate in the nucleus e.g. adenoviruses
using cellular proteins. Poxviruses replicate in
the cytoplasm and make their own enzymes
for nucleic acid replication. (Adenoviruses;
Herpesviruses; Poxviruses, etc)
II: Single-stranded (+)sense DNAII: Single-stranded (+)sense DNA
Replication occurs in the nucleus
involving the formation of a (-)sense strand,
which serves as a template for (+)strand RNA
and DNA synthesis. e.g. (Parvoviruses).
III: Double-stranded RNAIII: Double-stranded RNA
These viruses have segmented genomes.
Each genome segment is transcribed
separately to produce monocistronic mRNAs.
IIV: Single-stranded (+)sense RNAV: Single-stranded (+)sense RNA
Naked RNA is infectious, no involvement of
virion particle associated polymerase. e.g.
V: Single-stranded (-)sense RNAV: Single-stranded (-)sense RNA
Must have a virion particle RNA directed
RNA polymerase. e.g. (Orthomyxoviruses,
VI: Single-stranded (+)sense RNA with DNAVI: Single-stranded (+)sense RNA with DNA
intermediate in life-cycleintermediate in life-cycle (RT-RNA-virus)(RT-RNA-virus)
Genome is (+)sense but unique among viruses
in that it is DIPLOID, and does not serve as
mRNA, but as a template for reverse
transcription. e.g. (Retroviruses)
VII: Double-stranded DNA with RNAVII: Double-stranded DNA with RNA
This group of viruses also relies on reverse
but unlike the Retroviruses, this occurs inside
the virus particle on maturation. On infection
of a new cell, the first event to occur is repair
of the gapped genome, followed by
transcription. e.g. (Hepadnaviruses).
Anti HIV drugsAnti HIV drugs
Nucleoside reverse transcriptase inhibitors
Non-nucleoside reverse transcriptase
Other viral drugsOther viral drugs
Viral DNA polymerase inhibitors
Inhibitor of viral uncoating and viral assembly
Nucleoside Reverse trancriptaseNucleoside Reverse trancriptase
This include group of drugs which are
nucleoside analogue e.g. analogue of
thymidine, adenosine,cytosine,guanosine. All
are phosphorylated by host cell enzymes to
give the 5-triphosphate. This compete with
host nucleosides which are essential substrate
for the formation of proviral DNA by viral
reversetrancriptase. So, incorporation of
analogues of nucleosides into growing viral
DNA chain thus terminating the chain.
Zidovudine and stavudine(analogue of
Didanosine(analogue of deoxyadenosinea)
Lamvidine(analogue of cytosine)
Abacavir(analogue of guanosine)
Non nucleoside reversetranscriptaseNon nucleoside reversetranscriptase
These are chemically diverse compounds that
are not nucleosideanalogue but blocks reverse
transcriptase by binding near the catalytic site
and denature it. Drug examples are
Protease inhibitorsProtease inhibitors
Protease is an enzyme present in HIV virus that
converts the polyprotiens into various
structural and functionalprotins by cleavage at
the appropriate positions. The drug target this
enzyme and viral replication stops.
Entry inhibitorsEntry inhibitors
It inhibits entry of virus into the host cell by
inhibiting the conformational change in
glycoproteins of virus that is necessary for
attachment to the receptors on host cell.
Integrase inhibitorsIntegrase inhibitors
Inhibits the integration of viral DNA into the
host cell DNA
Viral DNA polymerase inhibitorsViral DNA polymerase inhibitors
Viral DNA polymerase inhibitors prevent the
replication by blocking DNA polymerase
either by nucleoside or non-nucleoside
Nucleoside analogueNucleoside analogue
aciclovir, cidofovir, famciclovir, ganciclovir,
idoxuridine, penciclovir, ribavarin,
Non nucleoside analogueNon nucleoside analogue
Inhibitor of viral uncoating and viralInhibitor of viral uncoating and viral
A viral membrane protien M2 functions as an
H+ ion channel in two steps of replication
When fusion of viral membrane and endosome
Assembly and release of virion
Inhibition of this protein inhibits viral uncoating
Amantadine and rimantadine
Neuraminidase inhibitorsNeuraminidase inhibitors
Neuraminidase is an enzyme present in virus
that helps in budding of new virus from
infected cell. Neuraminidase inhibitors inhibits
Biologics and immunomodulatorsBiologics and immunomodulators
Immunomodulators enhance the host defence.
Pooled immunoglobulin contains antibodies
against various viruses which are directed
against virus envelop and can neutralize some
viruses and prevent their attachment to host
e.g. interferon-α, pegylated interferon-α, inosine
•It is effective against a broad spectrum of DNA
and RNA viruses for example severe RSV
infection in children.
• It is used in combination with interfero-a-2b to
eliminate chronic hepatitis C infection.
Mechanism of actionMechanism of action
• MOA of ribavirin is studied on influenza virus.
• The drug is first converted to ribivirin-
triphosphate (5 phosphate derivative), which
exerts its antiviral action
By inhibiting the guanosine-triphosphate
Preventing viral mRNA capping
Blocking RNA-dependent RNA polymerase
• Ribavirin is effective orally and intravenously
• Absotion is increased if drug is taken with fatty meal
• Aerosol is used in certain respiratory viral infections
e.g in the treatmen of RSV infection.
• The drug is retained in all tissues except brain
• Drug and its metabolite are eliminated in the urine.
Adverse effectsAdverse effects
• When given orally and intravenously:
Dose dependent transient anemia
• When given through aerosol it is safer but can
Deteriorate the respiratory function of infants.
Therefore monitoring is essential.
• Teratogenic effects so contraindicated in pregnancy
Naturally occurring inducible glycoprotein
Interfere with ability of viruses to infect cells
Synthetically prepared by Recombinant DNA
Three types Exist ▪ Alpha ▪ Beta ▪ Gamma
Interferon alpha-2b has been approver for the treatment
of Hepatitis B & C, Condylomata acuminata and Cancer
Interferon Beta has some effectiveness in treatment of
Mode of Action
Induction of host cell enzymes
Inhibit Viral RNA translation leading to
degradation of Viral mRNA & tRNA
The Exact mechanism is incompletely understood
Not active orally, but can be administered
Intralesionally ▪ Subcutaneously ▪Intravenously
Little active form is found in plasma
Metabolized in Liver
Cellular uptake and metabolism by Liver and
Kidney cause disappearance from plasma
Negligible Renal elimination
Flu-like symptoms (Fever, Chills, Myalgias, Arthralgias,
Bone marrow suppression including
Hypersensitivity reaction and Hepatic failure are rare
It has greater specificity than Vidarabine
against herpes viruses.
Use in the treatment of choice in HSV
encephalitis and increase rate of survival.
It is given prophylactically to sero +ve patients
before bone marrow & after heart transplants.
Mechanism of actionMechanism of action
Acyclovir, is a guanosine analog that lacks a true
It is monophosphorylated in the cell by herpes
virus encoded enzyme thymidine kinase.
Monophosphorylated analog is converted to di &
triphosphate forms by the host cells.
Acyclovir triphosphate competes with
deoxyguanosine triphosphate as a substrate for
viral DNA polymerase & is itself incorporated
into the viral DNA
It cause premature DNA chain termination.
Irreversible binding of acyclovir containing
template primer to viral DNA polymerase
inactivate the enzyme.
The drug is less effective against the most
It is administered by intravenous, oral, tropical
It distributes well throughout the body
It is partially metabolize to an inactive
Excretion into the urine occurs both by
glomerular filtration & by tubular secretion.
It is accumulates in patients with renal failure.
The valyl ester,valacyclovir has greater oral
bioavailability than acyclovir.
This easter is rapidly hydrolyzed to acyclovir
& achieves levels of the later comparable to
those from i.v acyclovir administration..
Adverse EffectsAdverse Effects
Adverse effects depends upon route of
Local irritation may occur from topical
head,diarrhea,nausia,&vomiting may result
after oral administration.
Transient renal dysfunction may occur at high
doses or in dehydrated patient receiving the
High dose of Valacyclovir can cause
gastrointestinal problems &thrombotic
thrombocytopenia purpura in patients with
Altered or deficient thymidine kinase &DNA
polymerases have been found in some resistant
It is most commonly isolated from
Cross resistance to other cyclovirs occurs.
It is an HIV infusion inhibitor,the first of the
novel class of antiretroviral drugs used in the
combination therapy for the treatment of HIV-1
Mechanism of actionMechanism of action
It works by disrupting HIV-1 molecular
machinery at the final stage of infusion
with the target cell,preventing uninfected
cells from being infected..
HIV binds to the host CD4+ cell via a viral
transmembrane protein, then undergoes a
conformational change that assists in the
fusion of viral membrane to the host cell
membrane. Enfuviritide binds to the viral
transmembrane protein preventing the creation
of an entry pore for the capsid of the virus,
keeping it out of the cell.
Clinical useClinical use
The drug is generally given by subcutaneous
injection in combination with others to treat
HIV infection when resistance become a
problem or when the patient is intolerant of
Enfuvirtide is a synthetic peptide and is thus
not bioavailable orally. Following a twice-
daily subcutaneous injection of 30 to 90 mg,
its bioavailability is approximately 84.3%.
Comparable absorption of the 90-mg dose has
been reported in different injection sites of the
abdomen, thigh, and arm. The volume of
distribution is 5.5 liters, and the clearance rate
is 1.4 liters/hour.
Adverse effectsAdverse effects
Central effects such as
Alterations in mood
Drug drug interactionsDrug drug interactions
Clinical studies involving enfuvirtide are
limited. No clinically significant drug
interaction was reported when this medication
was used in combination with the other
antiretroviral drugs. In cell culture media
assays, enfuvirtide exhibited additive-to-
synergistic effects when it was combined with
individual members of various antiretroviral
agents, such as zidovudine AZT, Retrovir