Browsing Pathways

Telithromycin is an oral antibiotic drug that is a semi-synthetic erythromycin derivative. Telithromycin is metabolized in the liver by cytochrome P450 and 3A4 enzymes. Telithromycin penetrates the bacterial cell wall and acts on the ribosomal subunits to interfere with protein synthesis. These compounds act by binding to the 50S subunit of the 70S ribosomal subunit this in turn blocks protein elongation of the bacterial ribosome. Telithromycin binds to domains II and V of the 23S RNA of the 50S subunit of the ribosome. As a result, protein synthesis is inhibited, preventing bacterial growth and this may even kill the bacteria. Common side effects from taking Telithromycin include dizziness, headache, and taste disturbances, with the chance of experiencing more adverse effects such as diarrhea, nausea, vomiting, loose stools, abdominal pain, flatulence and dyspepsia.

Telithromycin is a semi-synthetic erythromycin derivative. It belongs to the chemical family called ketolides, a group belonging to the macrolide-lincosamide-streptogramin (MLS) class. Telithromycin prevents bacterial growth by inhibiting bacterial protein synthesis. Similar to macrolides, telithromycin directly blocks translation of the bacterial 23S ribosomal RNA; however, unlike macrolides, telithromycin also blocks bacterial ribosomal assembly (mechanism not shown). Telithromycin binds to two sites on the 50S ribosomal subunit, domains II and V of the 23S rRNA, whereas macrolides bind only to domain V. The C11-12 carbamate side chain is thought to contribute to a higher binding affinity of telithromycin compared to erythromycin A. In erythromycin A-susceptible bacteria, telithromycin exhibits 10 times greater affinity than erythromycin. Its relative binding affinity is further increased to 25 times greater in macrolide-resistant bacteria strains. This is likely due to the additional binding site on domain II since macrolide resistance occurs as a result of alterations in the domain V binding site.

Telbivudine is a synthetic thymidine nucleoside analog with specific activity against the hepatitis B virus. It is administered orally. Telbivudine is the unmodified β–L enantiomer of the naturally occurring nucleoside, thymidine. It undergoes phosphorylation via interaction with cellular kinases to form the active metabolite, telbivudine 5'-triphosphate. Telbivudine 5'–triphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate, thymidine 5'–triphosphate. This leads to the chain termination of DNA synthesis, thereby inhibiting viral replication. Incorporation of telbivudine 5'–triphosphate into viral DNA also causes DNA chain termination, resulting in inhibition of HBV replication. Telbivudine inhibits anticompliment or second-strand DNA. This causes DNA chain termination, preventing the growth of viral DNA. Less Viral DNA is transported into the nucleus, therefore, less viral DNA is integrated into the host DNA. Less viral proteins produced, fewer viruses can form.

Telaprevir is an NS3/4A viral protease inhibitor used in combination with other antivirals for the curative treatment of chronic Hepatitis C Virus infections. Hepatitis C virus lipoviroparticles enter target hepatocytes via receptor-mediated endocytosis. The lipoviroparticles attach to LDL-R and SR-B1, and then the virus binds to CD81 and subsequently claudin-1 and occludin, which mediate the late steps of viral entry. The virus is internalized by clathrin-dependent endocytosis. RNA is released from the mature Hepatitis C virion and translated at the rough endoplasmic reticulum into a single Genome polyprotein. Paritaprevir accumulates in the liver after uptake into hepatocytes via solute carrier organic anion transporter family member 1B1. Paritaprevir inhibits NS3/4A protease, which is an enzyme that cleaves the heptatitis C virus polyprotein downstream of the NS3 proteolytic site, which generates nonstructural proteins NS3, NS4A, NS4B, NS5A, and NS5B. These proteins are required in viral RNA replication, therefore because of the inhibition of their formation, RNA replication cannot occur. Because RNA replication does not occur, the mature virion is unable to form. At higher concentration above their antiviral half-maximal effective concentration (EC50), Paritaprevir and other NS3/4A inhibitors also restore interferon (IFN)-signaling pathways that are thought to be disrupted by NS3/4A protease and recover innate immune processes. NS3/4A protease cleaves two essential adaptor proteins that initiate signaling leading to activation of IFN regulatory factor 3 and IFN-α/β synthesis, which are mitochondrial antiviral-signaling proteins.