Neuraminidase inhibitors are antiviral drugs used to treat acute respiratory infections and influenza (a highly contagious viral infection that affects the respiratory system and is a major cause of morbidity and mortality) Zanamivir is approved for treatment of uncomplicated acute illness caused by influenza virus in persons aged greater than or equal to 12 years who have been symptomatic for no more than 2 days.

1. NEURAMINIDASE
INHIBITORS
JASERAH SYED
MSc - I

2. INTRODUCTION
 Neuraminidase also called sialidase,are a group of enzymes that cleave sialic acid,
a carbohydrate occurring on the surfaces of cells in humans and other animals and
also in plants and microorganisms.
 These enzymes are known to occur as Ags (foreign proteins that stimulate the
production of Abs) on the surfaces of certain viruses, namely those of the families
Orthomyxoviridae and Paramyxoviridae, as well as on the surfaces of some
infectious bacteria and other microorganisms.
 Neuraminidase cleaves the sialic acid molecule, thereby freeing the virus to infect
other cells in the host organism.
 Neuraminidase inhibitors inhibit the enzyme neuraminidase.
 They are commonly used as antiviral drugs because they block the function of viral
neuraminidases of the influenza virus, by preventing its reproduction by budding
from the host cell.

3. HISTORY
 The first Neuraminidase Inhibitors (NAIs) were synthesized in 1960s
by Edmond et al. through an attempt to understand the
catalytic mechanism of the neuraminidase enzyme.
 In early 1990s, the determination of biological crystal structure of
influenza virus surface protein led to the discovery of the active site
and provided the opportunities to discover and design new and
specific inhibitors.

4. NAI- A KEY DRUG
 Influenza neuraminidase has been established as a key drug target for the
treatment of influenza infections, predominantly for the following reasons:
A. Firstly, the structure of the influenza neuraminidase active site is highly
conserved between influenza A and B strains, making neuraminidase an
attractive target for the development of broad-spectrum inhibitors (Yen et
al. 2006).
B. Secondly, resistance to neuraminidase inhibitors develops less commonly
than to other anti-influenza drugs.
C. Thirdly, in contrast to adamantanes, neuraminidase inhibitors are mostly
well tolerated in patients under therapy.
D. Finally, neuraminidase protein is a freely accessible target for antiviral
molecules with an extracellular mode of action.

5. DIFFERENCE BETWEEN ADMANTASE
AND NEURAMINIDASE
NEURAMINIDASE
a) Effective against influenza A &
influenza B
b) Less toxic
c) Effective against all subtypes
of NA
ADMANTASE
a) Effective against only
influenza A & not influenza B
b) More toxic in comparison
c) Not effective against all
subtypes of NA

6. MECHANISM OF ACTION
 The neuraminidase inhibitors Zanamivir and Oseltamivir interfere with the
release of progeny influenza virus from infected host cells, a process that
prevents infection of new host cells and thereby halts the spread of infection
in the respiratory tract.
 Since replication of influenza virus in the respiratory tract reaches its peak
between 24 and 72 hours after the onset of the illness, drugs such as the
neuraminidase inhibitors that act at the stage of viral replication must be
administered as early as possible.

7. MECHANISM OF ACTION

8. SPECIFIC NA INHIBITORS
A. Laninamivir
B. Oseltamivir (Tamiflu)
C. Peramivir
D. Zanamivir (Relenza)

9. ZANAMIVIR
MODE OF ACTION –
• Zanamivir works by binding to the active site of
the neuraminidase protein, rendering the
influenza virus unable to escape its host cell and
infect others.
• It is also an inhibitor of influenza virus
replication in vitro and in vivo. In clinical trials,
zanamivir was found to reduce the time-to-
symptom resolution by 1.5 days if therapy was
started within 48 hours of the onset of
symptoms.

10. OSELTAMIVIR
 MODE OF ACTION –
• Oseltamivir is a neuraminidase inhibitor,
a competitive inhibitor of
influenza´s neuraminidase enzyme.
• The enzyme cleaves the sialic acid which is found
on glycoproteins on the surface of human cells, and
helps new virions to exit them.
• Thus oseltamivir prevents new viral particles from
being released.

11. PERAMIVIR
 MODE OF ACTION -
• Peramivir is a neuraminidase inhibitor, acting as
a transition-state analogue inhibitor of
influenza neuraminidase and thereby preventing new
viruses from emerging from infected cells.
• It is approved for intravenous administration.

12. USAGE
There are 2 subgroups of NA inhibitors that have been approved by regulatory
authorities in the US and Europe, Zanamivir and Oseltamivir. Both are for the
treatment and prevention of influenza.
 Laninamivir
Laninamivir is approved for the treatment of influenza. Laninamivir is a long acting
inhaled drug given as a prodrug . It is given as a single dose and remains active for
at least 5 days and up to 7 days.
 Oseltamivir
Oseltamivir can be found under trade names such as Antiflu, Fluvir, Fluhalt, , Omiflu,
Rimivat, Virobin, Oseltamivir and Tamiflu. Oseltamivir is used for patients 1 year and
older. It is given as one dose, twice a day for the treatment of influenza. In the
prevention of influenza, oseltamivir is given as one dose, once a day for at least 10
days after contacting with an infected person and up to six months . The most
common side effects of Oseltamivir are headache and nausea (in adults) and
vomiting, cough and nasal congestion (in children).

13.  Peramivir
Peramivir is approved for the treatment of influenza. It is used as
intravenous and was used in the emergency treatment of 2009 H1N1
in select patients.
 Zanamivir
Zanamivir is used for patients 5 years and older. It is given as one
10 mg dose, twice a day for the treatment of influenza. In the
prevention of influenza, zanamivir is given as one 10 mg dose, once a
day for 10 days after contacting with an infected person or up the 28
days. The most common side effect of Zanamivir is reported to be
rash.