Antiviral

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An antiviral agent (also known as an antiviral agent ; Latin virus and old Greek στάσις stasis "standstill" or antiviral active ingredient) is a substance that inhibits the multiplication of viruses . Antivirals are widely used as drugs in the treatment of infectious diseases ( viral infections ) caused by viruses .

Basics

Viruses do not have their own metabolism, which makes causal treatment of viral infectious diseases difficult. Treatment is often not necessary because viral infections often heal spontaneously. Antivirals are mainly used for infections in which the patient's immune system is unable to eradicate the virus on its own . A widespread use is currently not planned , taking into account the potential for side effects and the endeavor to avoid the development of resistance . The medicinally used substances against viruses only have a virostatic effect. This means that they only prevent the virus from multiplying through various mechanisms of action. Virucidal drugs - that is, drugs that kill viruses - do not currently exist, but there are virucidal disinfectants.

Development of antiviral agents

Since the virus replicates inside normal cells and is there very closely linked to the central biochemical cell mechanisms, the antiviral agents in question must either prevent the virions from penetrating the host cells, intervene in the cell metabolism to the detriment of virus replication, or after a possible virus replication in the cells prevent the escape of the new viruses from the cells.

On the other hand, these sought-after active ingredients must also be compatible with the body metabolism, the cell structure and / or the internal cell metabolism as a whole, since otherwise not only, for example, virus replication in the cells comes to a standstill, but in the worst case also the (cell) life of the entire organism being treated . Because these conditions are very difficult to reconcile, the antiviral drugs developed so far are often associated with serious side effects . This balancing act posed difficult tasks for medicine, which so far have mostly remained unsolved.

The development of effective antiviral active ingredients is also exacerbated by the development of resistance on the part of the viruses to be combated to a useful active ingredient once found, of which they are well able due to their extremely fast reproduction cycle and the biochemical nature of this replication.

Application of antiviral agents

An example of the very successful use of antivirals is modern HIV therapy, which is able to enable patients to live an almost normal life for many years under medical treatment through targeted combinations of active ingredients and structured side effect management. The survival time is significantly increased in comparison to untreated patients or patients with "classic" HIV therapy.

Classification of antiviral agents

Antivirals have different points of attack in the multiplication stages of a virus:

  • Prevention of the docking of the virus particles on the cell membrane of the host organism
  • Prevention of penetration into the host cell, prevention of uncoating (release of capsid and genome from the virus envelope )
  • Disruption / inhibition of the synthesis of viral nucleic acids and proteins (e.g. capsid proteins)
  • Inhibition of assembly (assembly of the synthesized virus components to form new viruses)
  • Suppression of the release of the newly formed viruses from the host cell
Stage for the virostatic attack Active ingredient group Virostatically active substances ( target virus )
Docking (adhesion) Entry Inhibitors Ancriviroc , Aplaviroc , Cenicriviroc , Enfuvirtide , Maraviroc , Vicriviroc ( HIV ), FGI-106 , LJ-001
Penetration, uncoating Penetration inhibitors Amantadine , Rimantadine ( Influenza A )

Pleconaril ( picornaviruses )

Nucleic acid synthesis, protein synthesis DNA polymerase inhibitors
  • Nucleosidic + nucleotide

Idoxuridine ( HSV )

Acyclovir , brivudine , famciclovir , penciclovir , sorivudine , valaciclovir ( HSV, VZV )

Cidofovir , Brincidofovir , Ganciclovir , Valganciclovir ( CMV )

  • other

Foscarnet ( HSV, CMV )

DNA / RNA polymerase inhibitors

Ribavirin , Taribavirin ( HRSV , HCV, and others )
Filibuvir , Nesbuvir , Sofosbuvir , Tegobuvir ( HCV )
Fosdevirin ( HIV )
RNA polymerase inhibitors

Favipiravir , JK-05 ( Influenza A )
BCX4430
Remdesivir ( EboV )

Reverse transcriptase inhibitors
  • Nucleosidic ( NRTI ) and nucleotide (NTRTI)

Abacavir , Didanosine , Elvucitabine , Emtricitabine , Fosalvudintidoxil , Fozivudintidoxil , Stavudine , Zalcitabine , Zidovudine ( HIV )

Lamivudine , lagociclovir , tenofovir ( HIV, HBV ) adefovir , alamifovir , clevudine , entecavir , pradefovir , telbivudine ( HBV )

Delavirdine , efavirenz , Emivirin , etravirine , Lersivirin , nevirapine , rilpivirine ( HIV )

Inosine monophosphate dehydrogenase inhibitors Merimepodib ( HCV )
Protease inhibitors

Amprenavir , Atazanavir , Brecanavir , Darunavir , Fosamprenavir , Indinavir , Lopinavir , Mozenavir , Nelfinavir , Ritonavir , Saquinavir , Tipranavir

Asunaprevir , Balapiravir , boceprevir , Ciluprevir , Danoprevir , Daclatasvir , Narlaprevir , telaprevir , Simeprevir , Vaniprevir

  • HRV protease inhibitors

Rupintrivir

Integrase inhibitors Elvitegravir , Dolutegravir , Raltegravir ( HIV )
Antisense oligonucleotides Fomivirsen ( CMV )
Recombinases
Helicase - primase inhibitors Amenamevir ( HSV , VZV )
Cyclophilin Inhibitors Alisporivir ( HCV )
Assembly Maturation inhibitors Bevirimat ( HIV )
Terminase inhibitors Letermovir ( CMV )
release Neuraminidase inhibitors Laninamivir , Oseltamivir , Peramivir , Zanamivir ( Influenza A, B )

In addition to substances that intervene directly in certain stages of virus replication and primarily target virus-specific structures, there are substances that target the structures of the host and have an antiviral effect by activating specific and unspecific immunological defense mechanisms .

These include cytokines such as alpha interferon (IFN-α) and beta interferon (IFN-β), as well as monoclonal antibodies ( immunoglobulins such as varicella immunoglobulin) and other immunomodulatory agents such as B. Imiquimod and Resiquimod .

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