Antiviral Agents

Structure Mechanism ADRs, Adverse effects Miscellaneous

Antiretroviral agents (ARV)
Nucleoside reverse transcriptase - Require host cell enzymes for anabolic phosphorylation to 5′-triphosphate
inhibitors (NRTIs) oiveoxynwaleoside nolog
: ☆
- Differ in intracellular activation pathway and toxicity
Abzeovin ( ABC )
- Myelosuppression - Effects on HIV-1, HIV-2,
Thymidine human lymphotropic
Zidovudine (ZDV, AZT)
analog (leukemia) virus (HTLV-1), and
other retroviruses
- Dose-limiting adverse effect : - Inhibits mitochondrial DNA
Thymidine
Stavudine (d4T) - Mostly 2′, 3′-dideoxynucleoside reversible sensory peripheral synthesis
analog
analogs  chain inhibitor neuropathy
Cytosine - Inhibit reverse transcriptase (RT) - Also treat chronic HBV
Lamivudine (3TC)
analog (Competitive inhibitors) infection
Cytosine - chemically related to
Emtricitabine (FTC)
analog lamivudine
- Nephrotoxicity - Ester prodrug : tenofovir
Adenosine
Tenofovir (TDF) disoproxil fumarate (TDF)
analog
- Also treat HBV
Non-Nucleoside Reverse Transcriptase
Polycyclic compounds with diverse chemical structures
Inhibitors (NNRTIs)
Nevirapine [ orp) Polycyclic - Binding site close to catalytic site - Stevens-Johnson syndrome
Efavirenz ( ] EFV compounds of RT (SJS)
Delavirdine with diverse - Restrict the mobility and - Toxic epidermal necrolysis
Bilpivirine [
RPr 3 chemical suppress the function of RT (TEN)
structures (noncompetitive inhibitors)
Protease Inhibitors (PIs) avin

Indinavir (IDV)
Saquinavir (SQV) - Dyslipidemia
Mimic natural - Hyperglycemia
React with catalytic site of protease ]
substrate - Insulin resistance
Ritonavir (RTV) = Inhibit viral maturation CYP450 inhibitor
(peptidomime - Lipodystrophy
Nelfinavir (NFV) (competitive inhibitors)
tics) (assoc. with metabolic abnormality ex.
Atazanavir (AZV) peptide, enzyme)
Lopinavir/ritonavir (LPV/r)
- Integrase Strand Transfer Inhibitor (INSTI)
Integrase Inhibitors
- Prevents the covalent insertion
(integration) of linear HIV DNA into
the host cell genome
- Prevents the formation of the HIV
Raltegravir
provirus
- Not inhibits human DNA
polymerase
- virus เข้า host cell โดย › Binding of CD4
Entry Inhibitors › Interaction with one of 2 chemokine receptors (CCR5 or CXCR4)
› Fusion of the viral and cell membranes
Maraviroc
Enfuvirtide
Antiherpes virus agents
- Acyclic guanine - Facilitated uptake and - require phosphorylation by
nucleoside analog phosphorylate by viral thymidine viral / host enzymes
- No 3′ hydroxyl kinase (TK) - Effective to HSV-1, HSV-2,
group as side - Affinity to viral TK = 200 x affinity VZV
Acyclovir (ACV) chain 3 to cellular TK  safe - Valacyclovir = L-valyl ester
Valacyclovir - [ACV-TP] in infected cells prodrug of acyclovir
Ba .
ioAne DNA = 40-100 x [ACV-TP] in normal cells (better bioavailability)
D 87
- Chain terminator
- Suicide inactivation emV
.

(acyclovir-incorporated DNA irreversibly

inhibits viral DNA polymerase)
- Acyclic guanine - Viral phosphotransferase : CMV - Myelosuppression - Effective to CMV (CMV -
nucleoside analog infection (encoded by UL97) › neutropenia retinitis, -enteritis, -colitis,
- GCV-TP › thrombocytopenia -pneumonia)
› inhibit viral DNA polymerase - Prevention of CMV infection
Ganciclovir (GCV)
(compete dGTP) in transplantation
› concentration in infected cells
= 10 x normal cells
› chain terminator

Anti-influenza agents ww .
enz .
aminidaseneur
- - Viral neuraminidase cleaves - No interference with
terminal sialic acid residues that influenza A vaccine
enables the virus to be released - Effective to Influenza A and
from the host cell B (include human and avian
- NAI leads to viral aggregation on H5N1 influenza virus)
cell surface, reduce virus release - Taken within 48 hr after
Neuraminidase
from cells onset of symptoms (acute
inhibitors (NAIs)
= Reduced infectivity and treatment) ; Duration = 5 days
Oseltamivir (P.O.)
Transmissibility -
Zanamivir (inhaler)
= Reduction in the severity of
symptoms, duration
= Reduction in secondary
complications (bronchitis,
pneumonia, otitis media and
sinusitis)

Anti-COVID-19 agents
- verted to active (favipiravir-RTP) - Teratogenic potential
Guanosine by intracellular kinase - Elevate Liver enzymes
Favipiravir (P.O.)
analogue - inhibit RNA-dependent RNA - Hyperuricemia
polymerase (RdRp)
- Converted to remdesivir - Reversible increase in -
triphosphate by intracellular kinase transaminases
Adenosine
Remdesivir (I.V.) – inhibit RNA-dependent RNA
analogue
polymerase (RdRp)