Antiviral drugs

Stages of viral life cycle

Entry/attachment → Uncoating → Genome replication → Assembly and maturation → Release and budding

Entry and attachment stage targeting drugs

Entry/fusion inhibitor

Uncoating stage drugs

Uncoating/M2 channel blockers

Genome replication stage drugs

Nucleoside/tide analogues, NNRTI/pyrophosphate analogue/integrase inhibitor

Assembly and maturation stage drugs

Protease inhibitor

Release and budding stage drugs

Neuraminidase inhibitors

Action of ___clovir drugs

Viral entry → Prodrug conversion into first active form by thymidine kinase → Cellular kinase change into final active form → Viral DNA termination

What is the advantage of targeting thymidine kinase

Thymidine kinase ONLY exist in viral infected cells; normal cells are spared

How does acyclovir triphosphate cause DNA termination

Competitive inhibition of DNA polymerase by mimicking dGTP

Incorporation = irreversible change → Immediate termination

Why is are valacyclovir and famciclovir preferred to acyclovir

Both have better oral bioavailability and have more convenient BID dosing; acyclovir has poor bioavailability requiring dosing up to 5x a day

When would aggressive IV intervention be indicated

Neonatal HSV, disseminated VZV and CNS, severe eczema herpeticum

How does treatment change with chronic suppression px

>=6 outbreak per year = chronic suppression; recommended that Px continue antiviral therapy even without symptoms or infection

How should drugs be administered in immunocompromised patients

DO NOT use standard duration → Oral/IV antivirals must be given until lesions are completely healed

Mechanism of acyclovir resistant HSV

Mutation or downregulation of thymidine kinase = antiviral cannot function

Foscarnet mechanism of action

Selective inhibition of DNA polymerase that DOES NOT need kinase activation

Cidofovir mechanism of action

Uses HOST kinase to activate into triphosphate state → Act on virus to inhibit DNA polymerase

Action of helicase primase inhibitors like pritelivir and amenamevir

Block DNA unwinding at replication fork → No primer synthesis

Oseltamivir mechanism of action

Prodrug → Liver activation into oseltamivir carboxylate → Neuraminidase inhibition

What is the consequence of neuraminidase inhibition

Sialic acid (bound to HA) is NOT cleaved by NA due to blocking by drug → Virus cannot leave the cell and spread

Paxlovid mechanism of action

Protease inhibitor of SARS-CoV-2