Pharmacology - Antiviral Drugs and and Retroviral Drugs
A virus gets into a cell by binding to the host cell's receptors. The receptor can defer depending on the type of virus and the type of enzymes used to reproduce either its own enzymes or that of the host. The virus cell such as HIV attaches to specific receptors in the host cell such as CD4 cells. HIV Virus usually tricks the CD4 receptor which usually binds to MHC Class 2 to activate T-helper cells to think that its substrates are the same as that of MHC Class 2. The Virus is then absorbed into the cell either by endocytosis of the viral particle or by bacteriophage injecting the DNA or RNA. In the cell, the virus will undergo uncoating releasing its nucleic material followed by protein and nucleic acid synthesis where the virus starts to use the mitochondria to produce more viral cells.
Antiviral drugs target specific regions in the process of reproduction and we should start with the absorption phase first. These drugs are Entry or Fusion inhibitors preventing the virus from getting into the cell of the host. The drugs include Enfuvirtide and Maraviroc. In the case of uncoating, drugs such as Amatindine and Rimantidine, prevent the uncoating of the viral nucleic acid. The next phase of thereproduction and colonization is nucleic acid synthesis and nucleic acid inhibitors which are reverse transcriptase inhibitors and non-nucleotide reverse transcriptase inhibitors, and Acyclovir. protease inhibitors can inhibit protein synthesis. In the Packaging and Assembly phase, Neuraminidase inhibitors such as oseltamivir, and Zanamivir.
Wikimedia
With Herpes virus drugs, they can be anti-metabolite and non-anti metabolites. With Anti-metabolites, drugs such as Gancyclovir, Acyclovir and Idoxuridine are used, while non-antimetabolite drugs include Foscarnet.
Gancyclovir is an analog of nucleosides that doesn't require the TK enzyme. While it can use it, it does not necessary require it. It is responsible for treating HSV, Varicella Zoster Virus, and Cytomegalovirus.
Acyclovir is a Purine Nucleoside Analogue which is converted by 3-phosphorylations to its active tryphosphate form. It requires its enzyme for its first phosphorylation but requires the host's cell kinases for its second and third phosphorylation. It is a substrate for viral DNA polymerase, it also cause chain termination. This drug is active against (Herpes simplex virus) HSV, Herpes Zoster Mucocutaneous HSV, Varicella Zoster Virus, Encephalitis caused by HSV, and . When administered IV, it can cause neurotoxicity, and Crystal Urea.
Idoxuridine is a thymidine analogue and it acts on DNA virus by inhibiting viral DNA synthesis. In can be used to treat HSV.
Foscarnet is a DNA and RNA polymerase inhibitor, it can be used instead of Gancyclovir. It doesn't require activation by the TK enzyme. It can give side effects such as nephrotoxicity which can lead to accute tubular necrosis, seizures, and acidosis.
HIV virus which is RNA as its genetic material but poccesses the RNA-dependent DNA-polymerase enzyme which converts the RNA to DNA copies which are inserted into the host cell. It's drug are to suppress HIV replication, prevent drug resistant strain from being reproduced, and prevent opportunistic infections. Anti-retroviral therapy is used to make this happen. These drugs are Reverse Treanscriptase inhibitor, fussion inhibitors, integrase inhibitor, and protease inhibitors.
With Fusion inhibitors, will block the GP41 to CD4 and the binding of GP120 to CCR5. GP41 to CD4 is inhibited using drugs such as Enfuvirtide which can be given IV, while GP120 to CCR5 is inhibited with drug such as Maraviroc which can be given orally.
The Reverse Transcriptase inhibitor which prevents the convertion of RNA into DNA then into the host cells can be divided into nucleoside analogue (NRTIs) and non-nucleoside analogue (NNRTIs). Nucleoside analogue drugs is effective on HIV1 and HIV2, while Non-nucleoside analogue drugs is effective on HIV1. Nucleoside analogue drugs are prodrugs need to be converted into triphosphate through cellular kinases and can suppress bone marrow. NRTI drugs includes Zidovudine which is given orally and it protects the cells that have not been infected by HIV. Other drug that can be used includes Lamivudine and Trazodone. NNRTIs are non-nucleoside drugs that act on the reverse transcriptase enzyme and inhibit the enzymes. Nevirapine and Efavirenz are two NNRTI drugs that act on only HIV-1. Nevirapine is a lipid-soluble drug that crosses the placenta helping to prevent transmission from mother to baby during pregnancy. Efavirenz works similarly to Nevirapine but has a longer half-life and its side effect includes daydreaming.
Protease Inhibitors inhibit aspartate protease which cleaves of precursor polypeptides to form the protein of matured HIV virus, therefore they cause the production of immature viruses by inhibiting the catalytic site. These drugs include Ritonavir, Indinavir, Nelfinavir, and Atazanavir. Integrase inhibitor drugs include Raltegravir which is effective in HIV-1 and HIV-2 with side effects that include headache, and nausea. At each phase of development, the anti-viral and anti-retroviral drugs are effective. These drugs will prevent the increase of viral load, and reduce the effect of opportunistic infections associated with this viruses.
https://www.ncbi.nlm.nih.gov/books/NBK548893/
https://www.ncbi.nlm.nih.gov/books/NBK551504/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463712/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327402/
https://www.ncbi.nlm.nih.gov/books/NBK556108/
https://go.drugbank.com/drugs/DB00249
Thanks for your contribution to the STEMsocial community. Feel free to join us on discord to get to know the rest of us!
Please consider delegating to the @stemsocial account (85% of the curation rewards are returned).
Thanks for including @stemsocial as a beneficiary, which gives you stronger support.