Mechanism of Action of Ribavirin in the treatment of Lassa Fever

PresentedBy

ADETUYI OLUWAFIJIMI YOMIBCH/08/4406

Department of Biochemistry,Federal University of Technology, Akure.

Lassa FeverLassa 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 daysInfection Rate in 2016: 254 people infected, 137 death recorded

Symptoms of Lassa FeverFever, malaise, fatigue and body aches.Nausea; vomiting; diarrhoea; headacheDiarrhoea; productive cough; proteinuria; low BP anaemia.Facial edema; convulsions; mucosal bleeding (mouth, nose, eyes); internal bleeding; confusion; disorientation; coma and death.

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

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

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 3and Mutagenesis.

Step 1:Ribavirin as Immunomodulator

Step 2: Inhibition of the enzyme inosine-monophospate-

dehydrogenase (IMPDH),

Guanosine monophosphate

Step 2 and 3: Inhibition of IMPDH and Mutagenesis

CONCLUSIONRibavirin 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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