This document outlines various antiviral agents, their targets and mechanisms of action. It discusses DNA synthesis/polymerase inhibitors for herpesviruses like aciclovir, ganciclovir and foscarnet. It also covers fusion inhibitors, adamantane derivatives and vaccines for viruses including VZV, CMV, HIV, HBV, HCV and influenza. Other agents discussed are interferons, ribavirin, monoclonal antibodies and immune response modifiers for treating viruses like RSV, HPV and HSV.

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TARGETS OF ANTI-VIRAL AGENTS

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ANTI-VIRAL AGENTS
Antiherpetic Agents
1. DNA Synthesis/ Polymerase Inhibitors
a. Thymidine Kinase
i. Purine Analog
□ guanine:
a) Aciclovir
b) Valaciclovir
c) Ganciclovir
d) Valganciclovir
e) Penciclovir
f) Famciclovir
□ adenine:
a) Vidarabine
ii. Pyrimidine Analog
□ uridine:
a) Idoxuridine
b) Trifluridine (aka Trifluoropyrimidine)
c) Edoxudine
□ thymine:
a) Brivudine
b) Sorivudine
□ cytosine:
a) Cytarabine
b. Not Thymidine Kinase activated
i. Foscarnet
2. Fusion Inhibitor
a. Docosanol (aka Behenyl alcohol)
3. Adamantane Derivative/ Matrix 2(M2) Proton Channel Inhibitor
a. Tromantadine
AntiVZV
a) DNA Synthesis/Polymerase Inhibitors
a. Thymidine Kinase activated
i. Purine Analog
□ guanine:
a) Aciclovir – for chickenpox
b) Valaciclovir – for shingles
c) Famciclovir
□ adenine:
a) Vidarabine
ii. Pyrimidine Analog
□ cytosine: Cytarabine
b) Antibodies/ Immune Globulin

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a. VZV Immune Globulin
c) VZV prophylaxis/Vaccines
a. Varicella vaccine - chickenpox vaccine
b. Zoster vaccine - a larger-than-normal dose of the vaccine used against
chickenpox; used in older adults to reduce the risk of shingles (herpes zoster) and
postherpetic neuralgia
d) Investigational AntiVZV
a. Valomaciclovir - viral DNA polymerase inhibitor; under clinical evaluation for
treatment of acute zoster and acute EBV infection (infectious mononucleosis)
AntiCMV
1. DNA Synthesis/ Polymerase Inhibitors
a. Thymidine Kinase activated
i. Purine Analog
□ guanine:
a) Ganciclovir
b) Valganciclovir
b. Not Thymidine Kinase activated
i. Foscarnet (aka Phosphonoformic acid)
c. Others
i. Cidofovir
ii. Brincidofovir (experimental prodrug of cidofovir)
2. Early Protein Synthesis Inhibitor
a. Fomivirsen - an antisense oligonucleotide antiviral; CMV treatment in
immunocompromised patients including those with AIDS
Antiretrovirals for HIV
1. N(A)RTIs
a. Abacavir - guanosine analog
b. Didanosine (ddI) - adenosine analog
c. Emtricitabine (FTC) - cytidine analog
d. Lamivudine (3TC) - cytidine analog
e. Stavudine (d4T) - thymidine analog
f. Zalcitabine (ddC) - cytidine analog
g. Zidovudine (ZDV, azidothymidine, AZT) - thymidine analog
2. Nt(A)RTIs
a. Tenofovir disoproxil fumarate (TDF) - adenosine analog
b. Tenofovir alafenamide fumarate (TAF)
3. NN(A)RTIs
a. 1st Generation
i. Delavirdine (DLV)
ii. Nevirapine (NVP)
iii. Efavirenz (EFV)
b. 2nd Generation (diarylpyrimidines)
i. Etravirine (ETR)
ii. Rilpivirine (RPV)

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iii. Doravirine (under development)
4. PIs
a. 1st Generation
i. Amprenavir (APV)
ii. Fosamprenavir (FPV)
iii. Indinavir (IDV)
iv. Lopinavir (LPV)
v. Nelfinavir (NFV)
vi. Ritonavir (RTV)
vii. Saquinavir (SQV)
b. 2nd Generation
i. Atazanavir (ATV)
ii. Darunavir (DRV)
iii. Tipranavir (TPV)
5. Entry/ Fusion Inhibitor
a. GP41 glycoprotein inhibitor
i. Enfuvirtide
b. CCR5 inhibitor
i. Maraviroc
6. INSTIs
a. Dolutegravir (DTG)
b. Elvitegravir (EVG)
c. Raltegravir (RAL)
d. Globoidnan A – a lignan from Eucalyptus globoidea; investigational
7. Pharmacokinetic Boosters
a. Ritonavir – w/ weak PI antiretroviral activity; enzyme inhibitor
b. Cobicistat – purely an enzyme inhibitor; notably used with elvitegravir
8. Ribavirin (aka Tribavirin)
a. MOAs:
i. nucleoside inhibitor (guanosine analog) that stops viral RNA synthesis and
viral mRNA capping
ii. a prodrug which when metabolized resembles purine RNA nucleotides,
interfering RNA metabolism
iii. R-5'-MP inhibits cellular IMP dehydrogenase, depleting intracellular GTP
pools
9. Investigational Antiretrovirals
a. Uncoating Inhibitors
i. TRIM5alpha gene
b. Transcription Inhibitors
i. Tat Antagonists
c. Translation Inhibitors
i. Trichosanthin
AntiHBV
1. N(A)RTIs
a. Entecavir (ETV) - guanosine nucleoside analog

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b. Lamivudine (3TC) - cytidine nuceloside analog
c. Telbivudine - thymidine nucleoside analog
d. Clebivudine - thymidine nucleoside analog
2. Nt(A)RTIs
a. Adefovir dipivoxil (ADV) - adenine nucleotide analog
b. Tenofovir disoproxil fumarate (TDF) - adenosine nucleotide analog
c. Tenofovir alafenamide fumarate (TAF)
AntiHCV
1. NS3/4A Serine Protease Inhibitor (-previr)
a. Asunaprevir (currently in Phase III)
b. Boceprevir
c. Grazoprevir
d. Faldaprevir (withdrawn from the market)
e. Paritaprevir (an acylsulfonamide)
f. Simeprevir
g. Telaprevir
2. NS5A Inhibitors (-asvir)
a. Daclatasvir
b. Elbasvir
c. Ledipasvir
d. Odalasvir (Phase III)
e. Ombitasvir
f. Ravidasvir (Phase III)
g. Samatasvir (Phase III)
h. Velpatasvir
3. NS5B RNA Polymerase Inhibitors
a. Beclabuvir (Phase III)
b. Dasabuvir
c. Deleobuvir (Never to Phase III)
d. Filibuvir (Never to Phase III)
e. Setrobuvir (Never to Phase III)
f. Sofosbuvir
g. Radalbuvir (Phase III)
4. Ribavirin (aka Tribavirin) – see Antiretrovirals for all observed MOAs
5. Investigational AntiHCVs
a. miR122 Inhibitor
i. Mivavirsen (an antisense oligonucleotide)
b. p7 Inhibitors
c. NS4B Inbibitors
d. Cyclophilin Inhibitors
Anti-Influenza
1. NIs/Sialic acid analogs/ Progeny Release Inhibitors
a. Oseltamivir – for Influenza A and B
b. Zanamivir – for Influenza A and B

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2. Adamantane Derivatives/ Matrix 2(M2) Proton Channel Inhibitors
a. Adapromine (1-(Adamantan-1-yl)propan-1-amine) - alkyl analog of rimantadine;
active vs Influenza A and B
b. Amantadine (1-aminoadamantane hydrochloride) - for Influenza A only
c. Rimantadine (1-(1-aminoethyl)adamantane) - for Influenza A only Anti-Influenza
3. Fusion/Entry Inhibitor
a. Umifenovir
i. chemically features an indole core, functionalized at all but one positions
with different substituents
ii. Other MOAs: (1) stimulation of humoral immune response, (2) induction
of interferon production, (3) stimulation of phagocytic function of
macrophages
4. Investigational Anti-Influenza
a. Peramivir - NI good for Influenza A and B (a cyclopentane analog)
b. Laninamivir octanoate - long-acting NI for Oseltamivir-resistant virus
c. DAS181 - host-directed antiviral agent that removes the virus receptor, sialic acid,
from adjacent glycan structures
Other Antiviral Agents
1. Interferons:
a. MOAs: inhibition of (1) viral penetration or uncoating, (2) mRNA synthesis, (3)
viral protein translation, (4) viral protein assembly and release
b. Indications: Venereal warts (condyloma acuminatum), chronic hepatitis B and C,
Kaposi's sarcoma, MS
c. PEG-Interferon - 40 kDa; has the advantage of sustained delivery and reduced
clearance of interferon
d. alpha and beta interferons - produced by all cells in response to viral infections;
effective against HBV, HCV, and HPV
e. gamma interferon - produced only by T lymphocyte and NK cells in response to
cytokines; has immune regulating effects; less antiviral activity as compared to
alpha and beta interferons
2. Ribavirin (aka Tribavirin) - also for RSV and Influenza A & B; see Antiretrovirals for all
observed MOAs
3. Palivizumab - Humanized IgG1 monoclonal antibody directed against an epitope in the A
antigen on the F surface protein of RSV
4. RNA interference therapeutic ALN-RSV01 - RSV treatment or prophylaxis
5. Benzodiazepine RSV604 - RSV treatment or prophylaxis
6. Immune Response Modifiers [Toll-Like Receptor 7 (TLR7) Activators]:
a. Imiquimod - topical treatment of external genital and perianal warts (i.e.,
condyloma acuminatum); Cells activated via TLR7 secrete cytokines (primarily
IFN-a), IL-6, and TNF-a
b. Resiquimod - antiviral and antitumor; topical gel for HSV and cutaneous T cell
lymphoma; adjuvant to increase vaccine effectiveness; several MOAs: (1) TLR7
activation, (2) TLR8 agonism, (3) upregulation of opioid growth factor receptor
(u-opioid receptor; regulates tissue growth, involved in embryonic development,
wound repair, and certain forms of cancer)

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c. Gardiquimod - structurally extremely similar to resiquimod differing only by an
oxygen for nitrogen switch