Antiviral Drugs

Question 1

Influenza virus

Answer 1

1. M2 Blockers
   - amantadine
   - rimantadine
2. Neuraminidase inhibitors
   - oseltamivir : oral
   - zanamivir: inhalation
   - peramivir : IV
3. Polymerase inhibitors
   - baloxavir marboxil: oral, active against influenza A, B, C and D viruses
   - favipiravir: oral, active against influenza A, B, and C viruses
   - pimodivir : oral, active against influenza A viruses only

Question 2

M2 blockers (MOA)

Answer 2

They inhibit the uncoating stage of infection by targeting the M2 proteins of all influenza A virus subtypes.

Activity against : ALL Influenza A subtypes !!

Question 3

Influenza Uncoating

Answer 3

1. M2 protein forms a pH-regulated (proton) channel in the viral membrane.
2. After internalization of the virus through endocytosis, the amantadine compounds are thought to block the (endosomal flow of protons) into the interior of the virion by interacting with the M2 transmembrane domain.
3. (Uncoating of the virus in the cytoplasm is inhibited), resulting in a block of viral infection.

Question 4

Neuraminidase inhibitors (MOA)

Answer 4

blocking the activity of the neuraminidase

Activity against: Influenza A and B viruses !! UNLIKE M2 BLOCKERS

Question 5

The viral neuramindase

Answer 5

It is an enzyme that cleaves the sialic acid from the haemagglutinin thus releasing the virus completely from the host cell.

Sialic acids are essential receptors that are bound by the viral hemagglutinin (HA) during attachment of the virus to the cell surface. By the time progeny virus bud, these receptors need to be removed to allow efficient release of the progeny viruses.

Question 6

SARS-CoV-2

Answer 6

• Nirmatrelvir : protease inhibitor
• Ritonavir : inhibiting the metabolism of nirmatrelvir through the inhibition of the liver enzyme cytochrome P450-3A4 (CYP3A)
• Paxlovid : indicated for the treatment of mild to moderate COVID-19 in people aged twelve years of age and older with SARS-CoV-2 infection, and who are at high risk for progression to severe COVID-19, including hospitalization or death. Within 5 days of initial infection was shown to reduce risk of long COVID.

The drug does not prevent infection in people who live with an infected person !!!!!

Question 7

Chronic Hepatitis C

Answer 7

1. Immunomodulators
2. Nucleoside Analogues
3. Direct-acting antivirals (DAAs)

Treatment is indicated for patients who are HCV-RNA positive and have elevated serum aminotransferases with histological moderate chronic hepatitis or more advanced lesions

Question 8

Immunomodulators (4)

Answer 8

IFN-a: 3 million IU, 3 times weekly

Peg-IFN-a: 180 mg per week

1. Stimulates the production of intracellular antiviral proteins like PKR
2. Increases the expression of MHC molecules
3. Stimulates NK cells
4. Stimulates cytotoxic T cells

Question 9

Nucleoside Analogues (3)

Answer 9

Ribavirin: 1000-1200 mg daily

1. Like adenosine or gunaosine, ribavirin can pair with either uridine or cytosine, inducing mutations in RNA-dependent replication in RNA viruses.
2. Inhibition of viral RNA-dependent RNA polymerase
3. Inhibition of inosine monophosphate dehydrogenase with consecutive intracellular deficiency of guanosine nucleotides

(The treatment of chronic hepatitis C using the combination of PEG-IFNa and Ribavirin results in SVR ranging from 40 to 70%.)

Question 10

Direct-acting antivirals (DAAs)