Mechanism of action of Ribavirin in the treatment of Lassa Fever

1. Mechanism of Action of Ribavirin
in the treatment of Lassa Fever
Presented
By
ADETUYI OLUWAFIJIMI YOMI
BCH/08/4406
Department of Biochemistry,
Federal University of Technology, Akure.

2. Lassa Fever
Lassa fever is an acute viral hemorrhagic fever caused by the
Lassa virus. The virus is named after the town-LASSA, in
Bornu State in Nigeria where the first cases occurred. It has
resulted in many small epidemics in Nigeria.
Vector: Rat and Human.
Incubation Period is 3 – 21 days
Infection Rate in 2016: 254 people infected, 137 death recorded
Symptoms of Lassa Fever
Fever, malaise, fatigue and body aches.
Nausea; vomiting; diarrhoea; headache
Diarrhoea; productive cough; proteinuria; low BP anaemia.
Facial edema; convulsions; mucosal bleeding (mouth, nose,
eyes);
internal bleeding; confusion; disorientation; coma and death.

3. Management of Lassa Fever
 Isolation
 Infection control – barrier nursing
 Ribavirin : shown to reduce mortality 5-10 fold if given
intravenously within 6 days of the clinical illness.
 Loading dose: IV 30mg/kg (max. 2g), followed by
15mg/kg 6hrly for 4 days (max. 1g), then 7.5mg/kg (max.
500mg) 8 hrly for 6 days
 Dilute Ribavirin in 150mls of 0.9%NS and infuse slowly.
 no convincing evidence that oral rivabirin delays or
prevents Lassa fever

4. Ribavirin
Ribavirin is a guanine analog that is phosphorylated by
adenosine kinase to its most active form, ribavirin-
triphosphate. This compound inhibits viral RNA-polymerase
preferentially at therapeutic doses by competing with
guanine-triphosphate for binding sites at the polymerase, as
well as inhibiting transferases necessary for the addition of
guanine.
Structure of Ribavirin and Guanosine

5. Mechanism of Action of Ribavirin
in the treatment of Lassa Fever
Stages of Action
Step 1
 Immunomodulation
Step 2
 Inhibition of the enzyme
inosine-monophospate-dehydrogenase (IMPDH),
Step 3
 and Mutagenesis.

6. Step 1:Ribavirin as Immunomodulator

7. Step 2: Inhibition of the enzyme inosine-monophospate-
dehydrogenase (IMPDH),
Guanosine monophosphate

8. Step 2 and 3: Inhibition of IMPDH and
Mutagenesis

9. CONCLUSION
Ribavirin has proven invaluable as a broad-spectrum antiviral drug
against many infections, including hepatitis C. The success of
ribavirin is attributable to its multivalent nature as a purine analogue
involved in multiple cellular pathways. Elucidation of the
mechanisms of action of ribavirin is important in understanding how
it can be used for the treatment of viral hemorrhagic fevers and the
development of new drugs.
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