Anti-Viral Drugs

Anti-influenza drugs

Influenza is a –ve sense RNA virus which has a lipid envelope with three key cell surface proteins:

–  Hemagglutinin (HA), Neuraminidase (NA), and a M2 ion channel.

– On entry, the envelope binds to the cell using HA which binds sialic acid

– M2 protein allows H+ inside acidifying vesicle, allowing endocytosis of the virus particle into the cell

– After replication is complete, neuraminidase cleaves sialic acid from surface allowing virus to leave cell

 

Therefore, anti-influenza drugs have specifically targeted these cell surface glycoproteins:

Amantadine + Rimantadine

These block the M2 ion channel to stop entry of virus particles

– They are used to treat influenza A early in infection

– Amantadine is also used to treat Parkinson’s as it blocks dopamine reuptake enhancing transmission

Ribavirin

This drug alters synthesis of GTP and inhibits the viral RNA polymerase to stop replication

– Used against influenza A and B, respiratory syncytial virus, hepatitis C

Side effects

• Haemolytic anaemia, cough and is avoided in pregnancy as it is teratogenic

Oseltamivir + Zanamivir

These are neuraminidase inhibitors which prevent the virus leaving cell

– They are used in the treatment and prophylaxis of influenza A and B.

Anti-herpes drugs

This is a group of double stranded DNA viruses which have a lipid envelope.

– They characteristically infect a cell but then establish a latent infection. Stimulation of the cell may then allow replication causing a secondary infection after a delay.

Drugs targeting herpesviruses typically target the viral DNA polymerase needed to replicate dsDNA.

– They are base analogs that lack a terminal 3-OH which means the strand can’t be elongated

 

Acyclovir

This is a purine analogue. It is phosphorylated by viral thymidine kinase and then terminates strand.

Ganciclovir

This is a purine analogue that is phosphorylated to the triphosphate form.

– It then inhibits the viral DNA polymerase to stop DNA replication

– Used to treat human cytomegalovirus and Herpesvirus

Side effects

• Neutropenia and thrombocytopenia

Cidofovir

This is a cytosine analogue which inhibits the DNA polymerase of cytomegalovirus

Side effects

• Nephrotoxic –> so given with Probenecid

Foscarnet

This inhibits cleavage of pyrophosphate during viral DNA polymerization

– Therefore, inhibits viral DNA and RNA polymerase

– Used to treat acyclovir resistant herpes infection

Anti-HIV drugs

These drugs take advantage of the fact that HIV is a retrovirus which must integrate into the host cell DNA:

– To enter the cell, the gp41 subunit of HIV binds to gp160 glycoprotein which is necessary for interaction with CD4 that lets HIV enter the cell

– This also requires a CCR5 chemokine to allow the conformational change to occur

– Once inside, the reverse transcriptase converts HIV RNA –> DNA to integrate into the genome

– The virus then uses an integrase enzyme to insert itself into the host DNA

– HIV translates proteins as one long polyprotein and uses a HIV protease to cut this into mature proteins 

HIV Fusion Inhibitors

Enfuvirtide

This binds gp41 subunit of HIV-1 to stop it from interacting with gp160 preventing entry

Maraviroc

This binds to host cells displaying CCR5 receptors preventing HIV entry into the cell.

Nucleoside Reverse Transcriptase Inhibitors 

e.g. Zidovudine/Azidothymidine (AZT)

These are thymidine analogues which get incorporated into the DNA strand but lack a 3-OH group

– Therefore, they act as chain terminators, preventing DNA synthesis

– Given with hydroxyurea –> this stops ribonucleotide reductase stopping host pyrimidine synthesis to boost activity of these drugs 

Side effects

• Peripheral Neuropathy (+ specific effects for each drug)

Non-Nucleoside Reverse Transcriptase Inhibitors

e.g. Nevirapine

These bind away from the active site of the reverse transcriptase and cause a conformational change of shape in the enzyme inhibiting its function

Side effects

• Induction of the CYP450 enzyme + Skin rash (Stevens-Johnson Syndrome)

Integrase inhibitors

e.g. Raltegravir (suffix = -gravir)

These inhibit the integrase to stop the virus integrating its newly made DNA into the host DNA

HIV protease inhibitors

e.g. Saquinavir + Ritonavir (suffix = -avir)

These inhibit the HIV-1 protease to stop polyprotein cleavage and virus maturation

– Protease inhibitors are recommended to be used in parallel with nucleoside analogues

– They have been shown to delay the progression of AIDs and recent evidence implies that disease may even be reversed to some degreed by adequate combination therapy.

Side effects

• Metabolic changes –> Diabetes + Hyperlipidaemia + weight gain

• Cytochrome P450 inhibition

Disclaimer

The intended purpose of this website is to be used as a resource for revision for exams. It should not be used as a guideline or reference for clinical practice/decision making or by patients looking for medical information or advice. In2Med takes no responsibility for any loss or damaged resulting from the use of information from this website.

Applying for the SFP?

 

Check out our SFP crash course!