PathWhiz

PathWhiz ID	Pathway	Meta Data
PW127459 View Pathway	drug action Foscarnet Action Pathway Homo sapiens Foscarnet is an antiviral used to treat CMV, HIV, and HSV infections. Foscarnet is an organic analogue of inorganic pyrophosphate that inhibits replication of herpes viruses in vitro including cytomegalovirus (CMV) and herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). Foscarnet does not require activation (phosphorylation) by thymidine kinase or other kinases and therefore is active in vitro against HSV TK deficient mutants and CMV UL97 mutants. Foscarnet exerts its antiviral activity by a selective inhibition at the pyrophosphate binding site on virus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases. Foscarnet inhibits the activity of DNA polymerase by competing with its substrate dGTP. Less viral proteins produced, fewer viruses can form. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: February 27, 2023 at 16:30 Last Updated: February 27, 2023 at 16:30
PW127460 View Pathway	drug action Valacyclovir Action Pathway Homo sapiens Valaciclovir (valacyclovir), also known as the brand name Valtrex, is an guanine nucleoside antiviral used to treat herpes exacerbations. Valaciclovir is the L-valine ester of aciclovir. Valacyclovir is rapidly and almost completely converted in man to aciclovir and valine, likely by the enzyme valacyclovir hydrolase. Aciclovir is transported from the liver into the blood via a drug transporter, then into the effected cells. Acyclovir is a guanosine analog used to treat herpes simplex, varicella zoster, herpes zoster, herpes labialis, and acute herpetic keratitis. Acyclovir is becomes acyclovir monophosphate due to the action of viral thymidine kinase.5 Acyclovir monophosphate is converted to the diphosphate form by guanylate kinase.1 Acyclovir diphosphate is converted to acyclovir triphosphate by nucleoside diphosphate kinase, pyruvate kinase, creatine kinase, phosphoglycerate kinase, succinyl-CoA synthetase, phosphoenolpyruvate carboxykinase and adenylosuccinate synthetase. Acyclovir triphosphate inhibits the activity of DNA polymerase by competing with its substrate dGTP. Acyclovir triphosphate also gets incorporated into viral DNA, but since it lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, 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. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: February 28, 2023 at 10:21 Last Updated: February 28, 2023 at 10:21
PW127461 View Pathway	drug action Brivudine Action Pathway Homo sapiens Brivudine is a drug used to treat herpes zoster. Although not approved in the U.S. or Canada, it is approved in several European countries. Brivudine exerts its antiviral activity by a selective inhibition at the pyrophosphate binding site on virus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases. Foscarnet inhibits the activity of DNA polymerase by competing with its substrate dGTP. Less viral proteins produced, fewer viruses can form. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: February 28, 2023 at 16:00 Last Updated: February 28, 2023 at 16:00
PW127462 View Pathway	drug action Brincidofovir Action Pathway Homo sapiens Brincidofovir is an oral lipid prodrug of cidofovir used in the treatment of human smallpox disease. It is a lipid conjugate pro-drug of the acyclic nucleotide analogue cidofovir. . Brincidofovir is a pro-drug comprising cidofovir conjugated to a lipid molecule - the lipid component mimics an endogenous lipid, lysophosphatidylcholine, which allows the molecule to hijack endogenous lipid uptake pathways to enter infected cells. Following uptake, the lipid molecule is cleaved to generate cidofovir, which is then phosphorylated to generate the active antiviral compound, cidofovir disphosphate. Cidofovir acts through the selective inhibition of viral DNA polymerase. After incorporation into the host cell, cidofovir is phosphorylated by pyruvate kinases to the active metabolite cidofovir diphosphate. Cidofovir diphosphate inhibits herpesvirus polymerases at concentrations that are 8- to 600-fold lower than those needed to inhibit human cellular DNA polymerase alpha, beta, and gamma(1,2,3). Incorporation of cidofovir into the growing viral DNA chain results in reductions in the rate of viral DNA synthesis. 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. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: March 01, 2023 at 10:33 Last Updated: March 01, 2023 at 10:33
PW127464 View Pathway	drug action Idoxuridine Action Pathway Homo sapiens Idoxuridine is a pyrimidine analog antiviral used for the treatment of viral eye infections, including herpes simplex keratitis. In chemical structure idoxuridine closely approximates the configuration of thymidine. As a result, idoxuridine is able to replace thymidine in the enzymatic step of viral replication or "growth". The consequent production of faulty DNA results in a pseudostructure which cannot infect or destroy tissue. The virus infected cell may only be attacked during the period of active synthesis of DNA. This in turn inhibits thymidylate phosphorylase and viral DNA polymerases from properly functioning. The effect of Idoxuridine results in the inability of the virus to reproduce or to infect/destroy tissue. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: March 06, 2023 at 10:44 Last Updated: March 06, 2023 at 10:44
PW127465 View Pathway	drug action Amoxicillin Action Pathway Helicobacter pylori Amoxicillin is a penicillin derivative used for the treatment of infections caused by gram-positive bacteria, in particular streptococcal bacteria causing upper respiratory tract infections. Amoxicillin alone is indicated to treat susceptible bacterial infections of the ear, nose, throat, genitourinary tract, skin, skin structure, and lower respiratory tract. Amoxicillin is given with calvulanic acid to treat acute bacterial sinusitis, community acquired pneumonia, lower respiratory tract infections, acute bacterial otitis media, skin and skin structure infections, and urinary tract infections. Amoxicillin is given with omeprazole in the treatment of Helicobacter pylori (H. pylori) infection. Amoxicillin competitively inhibits penicillin-binding protein 1 and other high molecular weight penicillin binding proteins. Penicillin bind proteins are responsible for glycosyltransferase and transpeptidase reactions that lead to cross-linking of D-alanine and D-aspartic acid in bacterial cell walls. Without the action of penicillin binding proteins, bacteria upregulate autolytic enzymes and are unable to build and repair the cell wall, leading to bacteriocidal action. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Karxena Harford Created On: March 06, 2023 at 13:44 Last Updated: March 06, 2023 at 13:44
PW127466 View Pathway	drug action Telbivudine Action Pathway Homo sapiens 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. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: March 06, 2023 at 17:34 Last Updated: March 06, 2023 at 17:34
PW127470 View Pathway	drug action Valganciclovir Action Pathway Homo sapiens Valganciclovir is an antiviral medication used to treat cytomegalovirus (CMV) retinitis in patients diagnosed with acquired immunodeficiency syndrome (AIDS). Valganciclovir is a prodrug of ganciclovir. After administration, valganciclovir is rapidly converted to ganciclovir in the intestine or liver by intestinal or hepatic esterases.Ganciclovir is transported into the blood and to the infected cells. It is then converted to the active form by a virus-encoded cellular enzyme, thymidine kinase, which catalyzes phosphorylation of ganciclovir to ganciclovir monophosphate. Ganciclovir monophosphate is converted into the diphosphate by cellular guanylate kinase then into the triphosphate by a number of cellular enzymes. Ganciclovir triphosphate inhibits the activity of DNA polymerase by competing with its substrate dGTP. Ganciclovir triphosphate also gets incorporated into viral DNA, but since it lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, 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. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: March 07, 2023 at 09:43 Last Updated: March 07, 2023 at 09:43
PW127471 View Pathway	drug action Trifluridine Action Pathway Homo sapiens Trifluridine is a fluorinated pyrimidine nucleoside that is structurally related to idoxuridine and an active antiviral agent in ophthalmic solutions that is mainly used in the treatment of primary keratoxonjunctivitis and recurrent epithelial keratitis due to herpes simplex virus. It displays effective antiviral activity against Herpes simplex virus type 1 and 2. The mechanism of action of trifluridine as an antiviral agent has not been fully elucidated, but appears to involve the inhibition of viral replication. Trifluridine gets incorporated into viral DNA during replication in replacement of thymidine, which leads to the formation of defective proteins and an increased mutation rate. 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. Trifluridine also mediates antineoplastic activities via this mechanism; following uptake into cancer cells, trifluridine is rapidly phosphorylated by thymidine kinase to its active monophosphate form. It is further phosphorylated into trifluridine triphosphate, which is readily incorporated into the DNA of tumour cells in place of thymidine bases to perturb DNA function, DNA synthesis, and tumour cell proliferation. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: March 07, 2023 at 14:17 Last Updated: March 07, 2023 at 14:17
PW127473 View Pathway	drug action Entecavir Action Pathway Homo sapiens Entecavir, known as the brand name Baraclude, is a guanine analogue oral antiviral drug used in the treatment of chronic hepatitis B for patients with active viral replication, histological evidence of active disease, or persistent elevations in liver transaminases. Entecavir competes with the natural substrate deoxyguanosine triphosphate (dGTP), which functionally inhibits all three activities of HBV polymerase (reverse transcriptase). This inhibits base priming, reverse transcription from messenger RNA, and synthesis of the positive strand of BV DNA. Since less viral DNA is formed, less of this DNA is available in the nucleus to undergo transcription and translation, consequently, less viral proteins are formed. This reduces the formation of new viruses since there are fewer viral proteins. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: March 08, 2023 at 11:29 Last Updated: March 08, 2023 at 11:29