Appendix II

Current Antiviral Drugs Note that while this table is as extensive as was possible at the time of writing, it is not possible to provide details of all antiviral drugs that may be available worldwide since approval status and/or availability varies between countries. Some of the drugs listed (e.g. brivudine, inosine pranobex, rimantadine, and tromantadine) may be available in a limited range of countries.

About the chapter opener image Dengue Virus (Courtesy of the Research Collaboratory for Structural Bioinformatics Protein Data Bank and David S. Goodsell, The Scripps Research Institute, USA.)

Chemical name*

[(1R)-4-[2-amino-6(cyclopropylamino) purin-9-yl]-1cyclopent-2-enyl] methanol

2-amino-9-(2hydroxyethoxymethyl)-3,9-dihydro6H-purin-6-one

{[2-(6-amino-9H-purin9-yl)ethoxy]methyl} phosphonic acid

Adamantan-1-amine

Tetrahydrofuran-3yl[3-[(4-aminophenyl) sulfonyl-(2methylpropyl) amino]-1-benzyl2-hydroxy-propyl] aminomethanoate

Abacavir (Ziagen)

Aciclovir (Zovirax, Zovir)

Adefovir dipivoxil (Preveon, Hepsera)

Amantadine (Symmetrel)

Amprenavir (Agenerase) Human immunodeficiency virus (Retroviridae)

Influenza A virus (Orthomyxoviridae)

Protease inhibitor, replaced by fosamprenavir

Ion channel inhibitor, interferes with viral penetration and uncoating, may interfere with assembly

Reverse transcriptase inhibitor (nucleotide analog, chain terminator)

DNA polymerase inhibitor (nucleoside analog, chain terminator)

Herpes simplex virus, varicellazoster virus (Herpesviridae)

Hepatitis B virus (Hepadnaviridae)

Nucleoside analog reverse transcriptase inhibitor (chain terminator)

Mode of action

Human immunodeficiency virus (Retroviridae)

Virus target(s)

Oral

Oral

Oral

Oral, topical, intravenous

Oral

Route of administration

H2N

P

O

NH2

HO

HO

H2N

HN

N H

N

N

O

Structure

O

O

N

S

O

N

N

O

N

N

N

N

NH2

OH

N

N

NH2

H N

N

OH

O

OH

O

APPENDIX II

O

Drug name (Trade name**)

284 Current Antiviral Drugs

5-[(E)-2-bromoethenyl]1-4S,5R)-4-hydroxy5-hydroxymethyl) oxolan-2-yl]pyrimidine2,4-dione

[1-(4-amino-2-oxopyrimidin-1-yl)-3hydroxy-propan-2-yl] oxymethyl-phosphonic acid

(1R,5S,6R)-2,8dioxabicyclo[3.3.0] oct-6-yl]N-[(2S,3R)-4[(4-aminophenyl) sulfonyl-(2methylpropyl)amino]3-hydroxy-1-phenylbutan-2-yl]carbamate

Brivudine (Helpin, Zerpex, Zonavir, Zostex)

Cidofovir (Vistide)

Darunavir (Prezista)

DNA polymerase inhibitor (nucleotide analog)

Cytomegalovirus (Herpesviridae)

Protease inhibitor

DNA polymerase inhibitor (nucleoside analog)

Varicellazoster virus (Herpesviridae)

Human immunodeficiency virus (Retroviridae)

Protease inhibitor

Human immunodeficiency virus (Retroviridae)

Oral

Intravenous

Oral

Oral

HO

HO

HO

O

HN

P

O

N H

O

NH

Br

H N

O

H

H

O

NH2

N

OH N N H

O H N

N

OCH3

Current Antiviral Drugs

O

O

H

N

NH2

O

(S)

S

O

N

O

OH

O

HO

N

O

HO

CH3O

O

O

Methyl N-[(1S)-1[[[(2S,3S)-2-hydroxy3-[[(2S)-2- (methoxycarbonylamino)-3,3dimethyl-butanoyl] amino]-4-phenylbutyl]-[(4-pyridin2-ylphenyl)methyl] amino] carbamoyl]2,2-dimethyl-propyl] carbamate O

Atazanavir (Reyataz)

APPENDIX II 285

Human immunodeficiency virus (Retroviridae)

N-[2-[4-[3-(1methylethyl amino) pyridin-2yl] piperazin-1-yl] carbonyl-1H-indol-5-yl] methanesulfonamide

9-[5-(hydroxymethyl) oxolan-2-yl]-3H-purin6-one

Docosan-1-ol

8-chloro-5-(2cyclopropylethynyl)5-(trifluoromethyl)-4oxa-2-azabicyclo[4.4.0] deca-7,9,11-trien-3-one

Delavirdine (Rescriptor)

Didanosine (Videx)

Docosanol (Abreva)

Efavirenz (Sustiva, Stocrin) Human immunodeficiency virus (Retroviridae)

Herpes simplex virus (Herpesviridae) (and other enveloped viruses)

Non-nucleoside reverse transcriptase inhibitor

Fusion (entry) inhibitor

Nucleoside analog reverse transcriptase inhibitor (competitive and chain terminator)

Non-nucleoside reverse transcriptase inhibitor

Mode of action

Oral

Topical

Oral

Oral

Route of administration

Cl

HO

HO

O

O S

NH

Structure

F

H N

O

O

OO

F

F

N

N

N H

N H

O N

H N

N

O

N N

APPENDIX II

Human immunodeficiency virus (Retroviridae)

Virus target(s)

Chemical name*

Drug name (Trade name**)

286 Current Antiviral Drugs

4-amino-5-fluoro-1[2-(hydroxymethyl)1,3-oxathiolan-5-yl]pyrimidin-2-one

Acetyl-YTSLIHSLIEESQ NQQEKNEQELLELDKW ASLWNWF-amide

2-amino-9-[4-hydroxy3-(hydroxymethyl)2-methylidenecyclopentyl]-3H-purin6-one

4-[6-amino-5-bromo2-[(4-cyanophenyl) amino] pyrimidin4-yl]oxy-3,5dimethylbenzonitrile

[2-(acetyloxymethyl)4-(2-aminopurin-9-yl)butyl]acetate

Emtricitabine (Emtriva, Coviracil)

Enfuvirtide (Fuzeon)

Entecavir (Baraclude)

Etravirine (Intelence)

Famciclovir (Famvir) Herpes simplex virus, varicellazoster virus (Herpesviridae)

DNA polymerase inhibitor; prodrug of penciclovir

Non-nucleoside reverse transcriptase inhibitor

Reverse transcriptase inhibitor (nucleoside analog, multiple inhibitory stages)

Hepatitis B virus (Hepadnaviridae)

Human immunodeficiency virus (Retroviridae)

Subcutaneous

Fusion inhibitor (biomimetic peptide)

Human immunodeficiency virus (Retroviridae)

Oral

Oral

Oral

Oral

Nucleoside analog reverse transcriptase inhibitor (chain terminator)

Human immunodeficiency virus (Retroviridae)

S O

N

N O

N

O

O O

N N

N H

O

N

N

O

N

O

Br

NH2 NH2

HN

N

N

N

HO

N

H2N

HO

N

Structure too large to show in print. Please see http://www. garlandscience.com/viruses

HO

F

NH2

APPENDIX II Current Antiviral Drugs 287

Chemical name*

(21 base antisense phosphorothioate oligonucleotide)

Drug name (Trade name**)

Fomivirsen (Vitravene)

Cytomegalovirus (Herpesviridae)

Virus target(s)

Inhibits expression of the IE genes of cytomegalovirus (mechanism disputed)

Mode of action

Intravitreal

Route of administration

H2N

O

H2N

O

O

H2N

H2N

O

N

H N

N

H N

H N

N

N

H N

H N

N

N

O

N

O

N

O

N

O

N

O

N

O

N

O

N

O

N

O

N

O

O

O

O

O

O

O

O

O

O

O

O

O

S

S

S

S

S

S

S

S

HO

S

P O

O P O OH S

HO

P O

O P O OH S

HO

P O

O P O OH S

HO

P O

O P O OH S

HO

P O

O P O OH S

HO

P O

O P O OH S

HO

P O

O P O OH S

HO

P O

O P O OH S

HO

P O

HO HO

P O

O P O OH S

O

O

O

O

O

O

O

O

O P O OH S

S

HO

O

O

O

N

N

N

N

N

N

O

N

O

N

O

N

O

N

O

N

N

N

O

H2N

H2N

N

N

H2N

H2N

O

O

O

O

O

O

O

O

N

H2N

N

NH

N

NH

H N

H N

N

H N

H N

O

O

O

NH2

O

O

O

O

O

O

O

N

NH

H N

N

NH

N

NH

APPENDIX II

O

H 2N

Structure

288 Current Antiviral Drugs

[(2R,3S)-1-[(4aminophenyl) sulfonyl-(2methylpropyl)amino]3-{[(3S)-oxolan-]3-yl oxycarbonylamino}4-phenyl-butan-2-yl] oxyphosphonic acid

Trisodium phosphonoformate hexahydrate

2-amino-9-(1,3dihydroxypropan-2yloxymethyl)-3H-purin6-one propoxymethyl) guanine

1-[(2R,4S,5R)4-hydroxy-5(hydroxymethyl) oxolan-2-yl]-5-iodopyrimidine-2,4-dione

1-isobutyl-1H-imidazo [4,5-c]quinolin-4-amine

Fosamprenavir (Lexiva)

Foscarnet (Foscavir)

Ganciclovir (Cymevene, Cytovene, Vitrasert)

Idoxuridine (Herplex Liquifilm, Stoxil)

Imiquimod (Aldara)

Papillomaviruses (Papovaviridae)

Indirect action; stimulation of the innate immune system via Toll-like receptors

Incorporated into DNA, disrupts transcription and translation (nucleoside analog)

DNA polymerase inhibitor (competitive, nucleoside analog, chain terminator only after multiple incorporation)

Cytomegalovirus (Herpesviridae)

Herpes simplex virus (Herpesviridae)

Intravenous

DNA polymerase inhibitor (noncompetitive, at pyrophosphate binding site)

Herpes simplex virus, other human herpesviruses (Herpesviridae)

Topical

Ophthalmic

Oral, intravenous, intravitreal

Oral

Protease inhibitor

Human immunodeficiency virus (Retroviridae) (prodrug of and replacement for amprenavir)

N

HO

H2N

HO

O

H2N

N

N

O

Ii

OH

O

NH2

N

H N

P OH O

OH

O

N

N

S

N

O

O

N

O

NH

O

HO

O

P N H

O

OH

OH

HO

O

O O

APPENDIX II Current Antiviral Drugs 289

Chemical name*

1-[2-hydroxy-4-[(2hydroxy-2,3-dihydro1H-inden-1-yl) carbamoyl]-5-phenylpentyl]-4-(pyridin3-ylmethyl)-N-tertbutyl-piperazine-2carboxamide

9-[(2R,3R,4S,5R)3,4-dihydroxy-5(hydroxylmethyl) oxolan-2-yl]-3H-purin6-one (inosine) plus acetamidobenzoic acid and dimethylaminoisopropanol

(Antiviral protein)

L-2¢,3¢-dideoxy-3¢thiacytidine

Drug name (Trade name**)

Indinavir (Crixivan)

Inosine pranobex (Imunovir, isoprinosine)

Interferon alfa (IntronA, Roferon-A, Viraferon; pegylated as Pegasys, PegIntron, ViraferonPeg)

Lamivudine (Epivir) Human immunodeficiency virus (Retroviridae), Hepatitis B virus (Hepadnaviridae)

Hepatitis B virus (Hepadnaviridae), Hepatitis C virus (Flaviviridae), Papillomaviruses (Papovaviridae), Human herpesvirus 8 (Herpesviridae) Nucleoside analog reverse transcriptase inhibitor (chain terminator)

Stimulation of cellmediated immunity and induction of cellular antiviral state

Oral

Injection (inhaled)

Oral

Indirect action; stimulation of immune system (T cells)

N H

HO

O

N

OH

O

NH

N

N

OH

N

OH

OH N

OH

O

O

HO

O S O

N N

NH2

N

N

O

(Pegylated recombinant protein)

O

HO

HN

Structure

H N

APPENDIX II

Herpes simplex virus (Herpesviridae), Papillomaviruses (Papovaviridae)

Oral

Protease inhibitor

Human immunodeficiency virus (Retroviridae)

Route of administration

Mode of action

Virus target(s)

290 Current Antiviral Drugs

(4S,5R,6R)-5acetamido-4carbamimidamido-6[(1R,2R)-3-hydroxy-2methoxypropyl]-5,6dihydro-4H-pyran-2carboxylic acid

(2S)-N-[(2S,4S,5S)-5-{[2(2,6-dimethylphenoxy) acetyl]amino}-4hydroxy-1,6-diphenylhexan-2-yl]-3-methyl2-(2-oxo-1,3-diazinan1-yl)butanamide

4,4-difluoro-N-{(1S)-3[3-(3-isopropyl-5methyl-4H-1,2,4-triazol4-yl)-8-azabicyclo[3.2.1] oct-8-yl]-1-phenylpropyl} cyclohexanecarboxamide

Laninamivir

Lopinavir (with ritonavir as Kaletra)

Maraviroc (Selzentry) Human immunodeficiency virus (Retroviridae)

Human immunodeficiency virus (Retroviridae)

Influenza A and B (Orthomyxoviridae)

Oral

Oral

Protease inhibitor

Chemokine receptor antagonist (CCR5)

Inhaled

Neuraminidase inhibitor

NH

NH

O

NH

F F

O

H2N

NH H

O H O

N

O

HN O

O H

N H

H O

N

O

HN

O

OH

OH

OH

N N

N

APPENDIX II Current Antiviral Drugs 291

Chemical name*

2-[2-hydroxy3-(3-hydroxybenzoyl)amino4-phenylsulfanylbutyl]-N-tertyl1,2,3,4,4a,5,6,7,8,8ahydroisoquinoline-3oxamide

1-cyclopropyl-5,11dihydro-4-methyl-6Hdipyrido [3,2-b:2¢,3¢-e] [1,4] diazepin-6-one

(3R,4R,5S)-4acetylamino-5-amino3-(1-ethylpropoxy)1-cyclohexene-1carboxylic acid ethyl ester

(Monoclonal antibody)

2-amino-9-[4-hydroxy3-(hydroxymethyl) butyl]-3H-purin-6-one

Drug name (Trade name**)

Nelfinavir (Viracept)

Nevirapine (Viramune)

Oseltamivir (Tamiflu)

Palivizumab (Synagis)

Penciclovir (Denavir, Fenistil)

Non-nucleoside reverse transcriptase inhibitor

Human immunodeficiency virus (Retroviridae)

Herpes simplex virus (Herpesviridae)

Respiratory syncytial virus (Paramyxoviridae)

DNA polymerase inhibitor (nucleoside analog)

Uptake inhibitor (neutralizing antibody)

Neuraminidase inhibitor

Protease inhibitor

Human immunodeficiency virus (Retroviridae)

Oral

Injection

Oral

Oral

Oral

Route of administration

H2N

HN

O

N

H N

N

HO

N

O

S

H N

O

O

N H

O

O

N

N NH2

NH

N

OH

OH

(Humanized monoclonal antibody)

O

N

O

H

H

Structure

OH

APPENDIX II

Influenza A and B (Orthomyxoviridae)

Mode of action

Virus target(s)

292 Current Antiviral Drugs

Human immunodeficiency virus (Retroviridae)

Respiratory syncytial virus (Paramyxoviridae), Lassa fever virus (Arenaviridae), yellow fever virus, hepatitis C virus (Flaviviridae) (in combination with interferon alfa), other viruses inhibited in vitro

N-(2-(4-(4-fluorobenzylcarbamoyl)-5-hydroxy1-methyl-6-oxo-1, 6-dihydro-pyrimidin2-yl)propan-2-yl)5-methyl-1,3,4oxadiazole-2carboxamide

1-b-Dribofuranosyl-1,2,4 triazole 3-carboxamide

1-(1-adamantyl) ethanamine

Raltegravir (Isentress)

Ribavirin (Copegus, Rebetol, Ribasphere, Vilona, Virazole, and generics)

Rimantadine (Flumadine)

Influenza A (Orthomyxoviridae)

Influenza A and B (Orthomyxoviridae)

(1S,2S,3S,4R)-3[(1S)-1-acetamido2-ethyl-butyl]-4(diaminomethylideneamino)-2hydroxy-cyclopentane1-carboxylic acid

Peramivir

Oral

Oral, inhaled

Several proposed, none certain (ribonucleoside analog)

As amantadine

Oral

Intravenous

Integrase inhibitor

Neuraminidase inhibitor

H3C

HO

H 3C

HN

O

O

N

N

H

OH

N

NH2

HN H H N

H

N

N N

O

O H C CH 3 3

H N

N

OH

OH

H3C

O

OH

O

NH2

N

O

O

OH H N

F

APPENDIX II Current Antiviral Drugs 293

1-[5-(hydroxymethyl)2,5-dihydrofuran2-yl]-5-methyl-1Hpyrimidine-2,4-dione

Stavudine (Zerit) Human immunodeficiency virus (Retroviridae)

Human immunodeficiency virus (Retroviridae)

N-[1-benzyl-2hydroxy-3-[3-(tertbutylcarbamoyl)1,2,3,4,4a,5,6,7,8,8adecahydroisoquinolin2-yl]-propyl]2-quinolin-2ylcarbonylaminobutanediamide

Saquinavir (Fortovase, Invirase)

Nucleoside analog reverse transcriptase inhibitor (chain terminator)

Oral

Oral

Oral

Route of administration

HO

O

S

HN

O

H3C

O

HN

H2N

N

Structure

HN

N

N

O

N

O

NH

O O OH

H N

OH H N

NH

O

O

O

N

H3C N

S

O

APPENDIX II

Protease inhibitor

Protease inhibitor

Human immunodeficiency virus (Retroviridae)

1,3-thiazol-5ylmethyl[3-hydroxy-5[3-methyl-2-[methyl[(2-propan-2-yl-1,3thiazol- 4-yl)methyl] carbamoyl]aminobutanoyl]amino-1,6diphenyl-hexan-2-yl] aminoformate

Ritonavir (Norvir)

Mode of action

Virus target(s)

Chemical name*

Drug name (Trade name**)

294 Current Antiviral Drugs

Herpes simplex virus (Herpesviridae)

Herpes simplex virus (Herpesviridae)

1-[4-hydroxy-5(hydroxymethyl) oxolan-2-yl]-5(trifluoromethyl) pyrimidine-2,4-dione

N-1-adamantyl-N[2-(dimethylamino) ethoxy] acetamide

Trifluorothymidine (trifluridine, Viroptic)

Tromantadine (Viru-Merz)

Alters glycosylation, disrupts virus entry and uncoating

Incorporated into DNA, disrupts transcription and translation (nucleoside analog)

Protease inhibitor

Human immunodeficiency virus (Retroviridae)

[R-(R*,R*)]-N-[3-[1-[5,6dihydro-4-hydroxy-2oxo-6- (2-phenylethyl)6-propyl-2H-pyran-3-yl] propyl]phenyl]-5(trifluoromethyl)-2pyridinesulfonamide

Tipranavir (Aptivus)

Nucleotide analog reverse transcriptase inhibitor (chain terminator)

Human immunodeficiency virus (Retroviridae)

({[(2R)-1-(6-amino-9Hpurin-9-yl)propan2-yl]oxy}methyl) phosphonic acid

Tenofovir (as tenofovir disoproxil fumarate, Viread)

Topical

Ophthalmic

Oral

Oral

O

HO

O

HN

F

F

N

N

O

F

F

O

O

N

HO O HO P

O

F

O

OH

F

S

H N

H3C

O

N

HO

N

N

O

N

NH NH22

O

N

APPENDIX II Current Antiviral Drugs 295

Chemical name*

2-[(2-amino-6-oxo3,9-dihydropurin-9-yl) methoxy]ethyl-2amino-3-methylbutanoate

2-[(2-amino-6-oxo3,6-dihydro-9Hpurin-9-yl)methoxy]3-hydroxypropyl (2S)-2-amino-3methylbutanoate

2-(6-aminopurin-9yl)-5-(hydroxymethyl) oxolane-3,4-diol hydrate

Drug name (Trade name**)

Valaciclovir (Valtrex)

Valganciclovir (Valcyte)

Vidarabine, adenosine arabinoside (Ara-A, Vira-A)

DNA synthesis inhibitor (unknown method, ribonucleoside analog)

DNA polymerase inhibitor (competitive; prodrug of ganciclovir)

Cytomegalovirus (Herpesviridae)

Intravenous, ophthalmic

Oral

Oral

Route of administration

HO

H2N

H2N

N

O

H N

N

OH

HN

O

Structure

OH

N

NH2

O

N

N

N N

O

O

N

O

H H2N HO

CH3

O

H3C

N

N

O

O

O

O

CH3

NH2 CH3

APPENDIX II

Herpes simplex virus, varicellazoster virus (Herpesviridae). Other viruses in vitro

DNA polymerase inhibitor (chain terminator; prodrug of acyclovir)

Mode of action

Herpes simplex virus, varicellazoster virus (Herpesviridae)

Virus target(s)

296 Current Antiviral Drugs

5-acetamido-4guanidino-6-(1,2,3trihydroxypropyl)-5,6dihydro-4H-pyran-2carboxylic acid

1-[(2R,4S,5S)-4-azido5-(hydroxymethyl) oxolan-2-yl]-5-methylpyrimidine-2,4-dione

Zanamivir (Relenza)

Zidovudine (Retrovir, Retrovis) Nucleoside analog reverse transcriptase inhibitor (chain terminator) Oral

Inhaled

Neuraminidase inhibitor

Influenza A and B (Orthomyxoviridae)

Human immunodeficiency virus (Retroviridae)

Oral

Nucleoside analog reverse transcriptase inhibitor (competitive and chain terminator)

Human immunodeficiency virus (Retroviridae)

O

N–- N+ N

O

HN

N

O

N

O

NH

NH2

O

H

OH

O HN

HO H N

HO

HO

HO

N

NH2

COOH

O

** Trade names used here are trademarks (™) or registered trademarks (®).

* The formal IUPAC naming system is used here for reasons of standardization, rather than the simpler and possibly more informative names that are sometimes used elsewhere (for example, in Figures 6.5 and 6.9).

4-amino-1-[(2R,5S)5-(hydroxymethyl) oxolan-2-y1]-1,2dihydropyrimidin-2one

Zalcitabine (Hivid)

APPENDIX II Current Antiviral Drugs 297