ATC Group: J05A Direct acting antivirals

Anatomical Therapeutic Chemical Classification System

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Direct acting antivirals

Hierarchical Position

Level
Code
Title
3
J05A
Direct acting antivirals

Contents

Active Ingredients

Chemical substance
Description

Abacavir is a potent selective inhibitor of HIV-1 and HIV-2. The mechanism of action as to HIV, is the inhibition of the enzyme reverse transcriptase of HIV, an event that causes chain termination and stopping the replication cycle of the virus.

Acyclovir is an antiviral agent with activity against herpes simplex virus and varicella-zoster virus. Acyclovir inhibits the DNA polymerase of the virus, preventing further proliferation.

Adefovir dipivoxil is an oral prodrug of adefovir, an acyclic nucleotide phosphonate analogue of adenosine monophosphate, which is actively transported into mammalian cells where it is converted by host enzymes to adefovir diphosphate. Adefovir diphosphate inhibits viral polymerases by competing for direct binding with the natural substrate (deoxyadenosine triphosphate) and, after incorporation into viral DNA, causes DNA chain termination.

Atazanavir is an azapeptide HIV-1 protease inhibitor (PI). The compound selectively inhibits the virus-specific processing of viral Gag-Pol proteins in HIV-1 infected cells, thus preventing formation of mature virions and infection of other cells.

Brivudine is a thymidine analogue with antiviral activity, indicated for the early treatment of acute herpes zoster in adult patients. Brivudine is incorporated into the viral DNA and blocks the action of DNA polymerases, thus inhibiting viral replication.

Cidofovir suppresses HCMV replication by selective inhibition of viral DNA synthesis. Biochemical data support selective inhibition of HSV-1, HSV-2 and HCMV DNA polymerases by cidofovir diphosphate, the active intracellular metabolite of cidofovir.

Daclatasvir is an inhibitor of nonstructural protein 5A (NS5A), a multifunctional protein that is an essential component of the HCV replication complex. Daclatasvir inhibits both viral RNA replication and virion assembly.

Darunavir is an inhibitor of the dimerisation and of the catalytic activity of the HIV-1 protease (KD of 4.5 × 10-12 M). It selectively inhibits the cleavage of HIV encoded Gag-Pol polyproteins in virus infected cells, thereby preventing the formation of mature infectious virus particles.

Dasabuvir is a non-nucleoside inhibitor of the HCV RNA-dependent RNA polymerase encoded by the NS5B gene, which is essential for replication of the viral genome. Co-administration of dasabuvir with ombitasvir/paritaprevir/ritonavir combines three direct-acting antiviral medicinal products with distinct mechanisms of action and non-overlapping resistance profiles to target HCV at multiple steps in the viral lifecycle.

Didanosine belongs to a class of medicines called nucleoside analogues or nucleoside reversetranscriptase inhibitors (NRTIs). Intracellularly, didanosine is converted by cellular enzymes to the active metabolite, dideoxyadenosine 5'-triphosphate. Dideoxyadenosine 5'-triphosphate inhibits the activity of HIV-1 reverse transcriptase both by competing with the natural substrate, deoxyadenosine 5'-triphosphate, and by its incorporation into viral DNA causing termination of viral DNA chain elongation.

Dolutegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral Deoxyribonucleic acid (DNA) integration which is essential for the HIV replication cycle.

Doravirine is a pyridinone non-nucleoside reverse transcriptase inhibitor of HIV-1 and inhibits HIV-1 replication by non-competitive inhibition of HIV-1 reverse transcriptase (RT). Doravirine does not inhibit the human cellular DNA polymerases α, β, and mitochondrial DNA polymerase γ.

Efavirenz is a NNRTI of HIV-1. Efavirenz is a non-competitive inhibitor of HIV-1 reverse transcriptase (RT) and does not significantly inhibit HIV-2 RT or cellular DNA polymerases (α, β, γ or δ).

Elvitegravir, is a type of antiviral agent called an ‘integrase inhibitor’. It blocks an enzyme called integrase, which is involved in a step in the reproduction of HIV. When the enzyme is blocked, the virus cannot reproduce normally, slowing down the spread of infection.

Emtricitabine is a synthetic nucleoside analogue of cytidine with activity that is specific to human immunodeficiency virus (HIV-1 and HIV-2) and hepatitis B virus (HBV).

Enfuvirtide is a member of the therapeutic class called fusion inhibitors. It is an inhibitor of the structural rearrangement of HIV-1 gp41 and functions by specifically binding to this virus protein extracellularly thereby blocking fusion between the viral cell membrane and the target cell membrane, preventing the viral RNA from entering into the target cell.

Εntecavir, a guanosine nucleoside analogue with activity against HBV polymerase, is efficiently phosphorylated to the active triphosphate (TP) form, which has an intracellular half-life of 15 hours. By competing with the natural substrate deoxyguanosine TP, entecavir-TP functionally inhibits the 3 activities of the viral polymerase: (1) priming of the HBV polymerase, (2) reverse transcription of the negative strand DNA from the pregenomic messenger RNA, and (3) synthesis of the positive strand HBV DNA.

Etravirine is an non-nucleoside reverse transcriptase inhibitors (NNRTI) of human immunodeficiency virus type 1 (HIV-1). Etravirine binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme’s catalytic site.

Famciclovir is the oral prodrug of penciclovir. Famciclovir is rapidly converted in vivo into penciclovir, which has in vitro activity against herpes simplex viruses (HSV types 1 and 2), varicella zoster virus (VZV), Epstein-Barr virus and cytomegalovirus.

Favipiravir is metabolized in cells to a ribosyl triphosphate form (favipiravir RTP) and that favipiravir RTP selectively inhibits RNA polymerase involved in influenza viral replication.

Fosamprenavir after oral administration, is rapidly and almost completely hydrolysed to amprenavir and inorganic phosphate prior to reaching the systemic circulation. Amprenavir binds to the active site of HIV-1 protease and thereby prevents the processing of viral gag and gag-pol polyprotein precursors, resulting in the formation of immature noninfectious viral particles.

Foscarnet is an antiviral agent with a broad spectrum inhibiting all known human viruses of the herpes group. Foscarnet exerts its antiviral activity by a direct inhibition of viral specific DNA polymerase a reverse transcriptase at concentrations that do not affect cellular DNA polymerases.

Ganciclovir, 9-(1,3-dihydroxy-2-propoxymethyl)guanine or DHPG, is a broadspectrum virustatic agent which inhibits the replication of viruses, including viruses of the herpes group, both in vivo and in vitro: herpes simplex types 1 and 2 (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes zoster (HZV).

Indinavir inhibits recombinant HIV-1 and HIV-2 protease with an approximate tenfold selectivity for HIV-1 over HIV-2 proteinase. Indinavir binds reversibly to the protease active site and inhibits competitively the enzyme, thereby preventing cleavage of the viral precursor polyproteins that occurs during maturation of the newly formed viral particle.

Inosine pranobex is a synthetic purine derivative with immunomodulatory and antiviral properties, which result from an apparent in vivo enhancement of host immune responses due to the drug.

Lamivudine is a nucleoside analogue which has activity against human immunodeficiency virus (HIV) and hepatitis B virus (HBV). Its main mode of action is as a chain terminator of viral reverse transcription.

Letermovir inhibits the CMV DNA terminase complex which is required for cleavage and packaging of viral progeny DNA. Letermovir affects the formation of proper unit length genomes and interferes with virion maturation. Letermovir is indicated for prophylaxis of cytomegalovirus (CMV) reactivation and disease.

Lopinavir is an inhibitor of the HIV-1 and HIV-2 proteases. Inhibition of HIV protease prevents cleavage of the gag-pol polyprotein resulting in the production of immature, non-infectious virus.

Lysozyme is a naturally occurring enzyme found in bodily secretions such as tears, saliva, and milk. It functions as an antimicrobial agent by cleaving the peptidoglycan component of bacterial cell walls, which leads to cell death.

Maraviroc is a member of a therapeutic class called CCR5 antagonists. Maraviroc selectively binds to the human chemokine receptor CCR5, preventing CCR5-tropic HIV-1 from entering cells.

Nelfinavir reversibly binds to the active site of HIV protease and prevents cleavage of the polyproteins resulting in the formation of immature non-infectious viral particles.

Nevirapine is a NNRTI of HIV-1. Nevirapine is a non-competitive inhibitor of the HIV-1 reverse transcriptase, but it does not have a biologically significant inhibitory effect on the HIV-2 reverse transcriptase or on eukaryotic DNA polymerases α, β, γ, or δ.

Ombitasvir is an nonstructural protein 5A (NS5A) inhibitor that acts by inhibiting the HCV protein NS5A.

Oseltamivir (oseltamivir carboxylate) is a selective inhibitor of influenza virus neuraminidase enzymes, which are glycoproteins found on the virion surface. Viral neuraminidase enzyme activity is important both for viral entry into uninfected cells and for the release of recently formed virus particles from infected cells, and for the further spread of infectious virus in the body.

Penciclovir has demonstrated in vivo and in vitro activity against herpes simplex viruses (types 1 and 2) and varicella zoster virus. Penciclovir triphosphate persists in infected cells for more than 12 hours where it inhibits replication of viral DNA and has a half-life of 9, 10 and 20 hours in cells infected with varicella zoster virus, herpes simplex virus type 1 and herpes simplex virus type 2 respectively.

Pibrentasvir is a pan-genotypic inhibitor of HCV nonstructural protein 5A (NS5A), which is essential for viral RNA replication and virion assembly.

Raltegravir is an integrase strand transfer inhibitor active against the Human Immunodeficiency Virus (HIV-1). Raltegravir inhibits the catalytic activity of integrase, an HIV-encoded enzyme that is required for viral replication. Inhibition of integrase prevents the covalent insertion, or integration, of the HIV genome into the host cell genome.

Ribavirin is a synthetic nucleoside analogue which has shown in vitro activity against some RNA and DNA viruses. The mechanism by which ribavirin in combination with other medicinal products exerts its effects against HCV is unknown.

Rilpivirine is a diarylpyrimidine non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1. Rilpivirine activity is mediated by non-competitive inhibition of HIV-1 reverse transcriptase (RT). Rilpivirine does not inhibit the human cellular DNA polymerases α, β and γ.

Ritonavir is an orally active peptidomimetic inhibitor of the HIV-1 and HIV-2 aspartyl proteases. Inhibition of HIV protease renders the enzyme incapable of processing the gag-pol polyprotein precursor which leads to the production of HIV particles with immature morphology that are unable to initiate new rounds of infection.

Saquinavir selectively inhibits the HIV protease, thereby preventing the creation of mature infectious virus particles. The HIV protease is an essential viral enzyme required for the specific cleavage of viral gag and gag-pol polyproteins.

Simeprevir is a specific inhibitor of the hepatitis C virus (HCV) NS3/4A serine protease, which is essential for viral replication. In a biochemical assay, simeprevir inhibited the proteolytic activity of recombinant genotype 1a and 1b HCV NS3/4A proteases, with median Ki values of 0.5 nM and 1.4 nM, respectively.

Sofosbuvir is a pan-genotypic inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication. Sofosbuvir is a nucleotide prodrug that undergoes intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), which can be incorporated into HCV RNA by the NS5B polymerase and acts as a chain terminator.

Stavudine, a thymidine analogue, is phosphorylated by cellular kinases to stavudine triphosphate which inhibits HIV reverse transcriptase by competing with the natural substrate, thymidine triphosphate. It also inhibits viral DNA synthesis by causing DNA chain termination due to a lack of the 3'-hydroxyl group necessary for DNA elongation. Cellular DNA polymerase γ is also sensitive to inhibition by stavudine triphosphate, while cellular polymerases α and β are inhibited at concentrations 4,000-fold and 40-fold higher, respectively, than that needed to inhibit HIV reverse transcriptase.

Telaprevir is an inhibitor of the HCV NS3•4A serine protease, which is essential for viral replication.

Telbivudine is a synthetic thymidine nucleoside analogue with activity against HBV DNA polymerase. It is efficiently phosphorylated by cellular kinases to the active triphosphate form. Incorporation of telbivudine-5'-triphosphate into viral DNA causes DNA chain termination, resulting in inhibition of HBV replication.

Tenofovir diphosphate inhibits HIV-1 reverse transcriptase and the HBV polymerase by direct binding competition with the natural deoxyribonucleotide substrate and, after incorporation into DNA, by DNA chain termination.

Tipranavir is a non-peptidic inhibitor of the HIV-1 protease that inhibits viral replication by preventing the maturation of viral particles.

Tromantadine is an antiviral medicine used to treat herpes simplex virus.

Valaciclovir, an antiviral, is the L-valine ester of aciclovir. Valaciclovir is rapidly and almost completely converted in man to aciclovir and valine. Aciclovir is a specific inhibitor of the herpes viruses with in vitro activity against herpes simplex viruses (HSV) type 1 and type 2, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr Virus (EBV), and human herpes virus 6 (HHV-6).

Valganciclovir is an L-valyl ester (prodrug) of ganciclovir. Ganciclovir is a synthetic analogue of 2'-deoxyguanosine and inhibits replication of herpes viruses in vitro and in vivo.

Velpatasvir is a HCV inhibitor targeting the HCV NS5A protein, which is essential for both RNA replication and the assembly of HCV virions. In vitro resistance selection and cross-resistance studies indicate velpatasvir targets NS5A as its mode of action.

Voxilaprevir is a pan-genotypic inhibitor of the HCV NS3/4A protease. Voxilaprevir acts as a noncovalent, reversible inhibitor of the NS3/4A protease.

Zalcitabine is a nucleoside analog reverse-transcriptase inhibitor (NRTI).

Zanamivir is a selective inhibitor of neuraminidase, the influenza virus surface enzyme. Neuraminidase inhibition occurred in vitro at very low zanamivir concentrations (50% inhibition at 0.64nM–7.9nM against influenza A and B strains).

Zidovudine is an antiviral agent which is highly active in vitro against retroviruses including the Human Immunodeficiency Virus (HIV).