Pathways

Lopinavir is an antiretroviral HIV-1 protease inhibitor used in combination with ritonavir to treat human immunodeficiency virus (HIV) infection. Lopinavir is marketed and administered exclusively in combination with ritonavir. This combination is necessary due to lopinavir's poor oral bioavailability and extensive biotransformation. The HIV virus binds and penetrates the host cell. Viral RNA is transcribed into viral DNA via reverse transcriptase. Viral DNA enters the host nucleus and is integrated into the host DNA via integrase. The DNA is then transcribed, creating viral mRNA. Viral mRNA is translater into the gag-pol polyprotein. HIV protease is synthesized as part of the Gag-pol polyprotein, where Gag encodes for the capsid and matrix protein to form the outer protein shell, and Pol encodes for the reverse transcriptase and integrase protein to synthesize and incorporate its genome into host cells. HIV-1 protease cleaves the Gag-pol polyprotein into 66 molecular species, including HIV-1 protease, integrase, and reverse transcriptase. Lopinavir inhibits HIV-1 protease. This inhibition prevents the HIV virion from fully maturing and becoming infective. Using the lipid bilayer of the host cell, a virus is formed and released. The inhibition of HIV-1 protease prevents the necessary molecular species from forming, therefore preventing maturation and activation of viral particles. This forms immature, non-infectious viral particles, therefore, Lopinavir prevents the virus from reproducing.

Ledipasvir is a direct-acting antiviral agent used to treat specific hepatitis C virus (HCV) infections in combination with other antiviral agents. 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. The genome polyprotein is cleaved by host and viral proteases into 10 viral proteins. The nucleocapsid protein core and the two envelope proteins E1 and E2 form the N terminus of the polyprotein and are the structural components of HCV virions. The precursor also gives rise to the viroporin p7 and six non-structural (NS) proteins. Ledipasvir is an inhibitor of the Hepatitis C Virus (HCV) Nonstructural protein 5A required for viral RNA replication and assembly of HCV virions. The exact mechanism of this protein is unknown. Although its exact mechanism of action is unknown, it is postulated to prevent hyperphosphorylation of NS5A which is required for viral production. Viral RNA replication complexes localize to lipid raft-containing, detergent-resistant membranes created by the viral protein NS4B. For full viral replication and maturation, replication complexes need to be in close proximity to lipid droplets, which requires the protein nonstructural protein 5A. Without the Lipid Droplet due to inhibition of nonstructural protein 5A, full viral RNA replication is unable to occur. Envelope glycoproteins are acquired through budding into the endoplasmic reticulum lumen. The immature, non-infective virions are released via the cellular golgi apparatus.

Ombitasvir is a direct acting antiviral agent used in combination with other antiviral agents for the treatment of Hepatitis C Virus (HCV) 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. The genome polyprotein is cleaved by host and viral proteases into 10 viral proteins. The nucleocapsid protein core and the two envelope proteins E1 and E2 form the N terminus of the polyprotein and are the structural components of HCV virions. The precursor also gives rise to the viroporin p7 and six non-structural (NS) proteins Ombitasvir is an inhibitor of the Hepatitis C Virus (HCV) Nonstructural protein 5A, which is required for viral RNA replication and assembly of HCV virions. The exact mechanism of this protein is unknown. Viral RNA replication complexes localize to lipid raft-containing, detergent-resistant membranes created by the viral protein NS4B. For full viral replication and maturation, replication complexes need to be in close proximity to lipid droplets, which requires the protein nonstructural protein 5A. Without the Lipid Droplet due to inhibition of nonstructural protein 5A, full viral RNA replication is unable to occur. Envelope glycoproteins are acquired through budding into the endoplasmic reticulum lumen. The immature, non-infective virions are released via the cellular golgi apparatus.

Daclatasvir is a direct-acting antiviral agent used to treat specific hepatitis C virus (HCV) infections in combination with other antiviral agents.Daclatasvir is a direct-acting antiviral agent that targets the nonstructural protein 5A (NS5A) and causes a decrease in serum HCV RNA levels. 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. The genome polyprotein is cleaved by host and viral proteases into 10 viral proteins. The nucleocapsid protein core and the two envelope proteins E1 and E2 form the N terminus of the polyprotein and are the structural components of HCV virions. The precursor also gives rise to the viroporin p7 and six non-structural (NS) proteins Daclatasvir is an inhibitor of the Hepatitis C Virus (HCV) Nonstructural protein 5A, which is required for viral RNA replication and assembly of HCV virions. The exact mechanism of this protein is unknown. Viral RNA replication complexes localize to lipid raft-containing, detergent-resistant membranes created by the viral protein NS4B. For full viral replication and maturation, replication complexes need to be in close proximity to lipid droplets, which requires the protein nonstructural protein 5A. Without the lipid droplet due to inhibition of nonstructural protein 5A, full viral RNA replication is unable to occur. Envelope glycoproteins are acquired through budding into the endoplasmic reticulum lumen. The immature, non-infective virions are released via the cellular golgi apparatus.

Elbasvir is a direct-acting antiviral medication used as part of combination therapy to treat chronic hepatitis C Elbasvir, when used in combination with grazoprevir as the combination product Zepatier, is indicated for use with or without ribavirin for the treatment of chronic HCV genotypes 1 or 4 infection in adults.7 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. The genome polyprotein is cleaved by host and viral proteases into 10 viral proteins. The nucleocapsid protein core and the two envelope proteins E1 and E2 form the N terminus of the polyprotein and are the structural components of HCV virions. The precursor also gives rise to the viroporin p7 and six non-structural (NS) proteins Elbasvir is an inhibitor of the Hepatitis C Virus (HCV) Nonstructural protein 5A, which is required for viral RNA replication and assembly of HCV virions. The exact mechanism of this protein is unknown. Viral RNA replication complexes localize to lipid raft-containing, detergent-resistant membranes created by the viral protein NS4B. For full viral replication and maturation, replication complexes need to be in close proximity to lipid droplets, which requires the protein nonstructural protein 5A. Without the lipid droplet due to inhibition of nonstructural protein 5A, full viral RNA replication is unable to occur. Envelope glycoproteins are acquired through budding into the endoplasmic reticulum lumen. The immature, non-infective virions are released via the cellular golgi apparatus.

Velpatasvir is a NS5A inhibitor used to treat chronic hepatitis C infections in patients without cirrhosis or with compensated cirrhosis, used as part of combination therapy to treat chronic Hepatitis C. Notably, velpatasvir has a significantly higher barrier to resistance than the first generation NS5A inhibitors, such as Ledipasvir and Daclatasvir, making it a highly potent and reliable alternative for treatment of chronic Hepatitis C. 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. The genome polyprotein is cleaved by host and viral proteases into 10 viral proteins. The nucleocapsid protein core and the two envelope proteins E1 and E2 form the N terminus of the polyprotein and are the structural components of HCV virions. The precursor also gives rise to the viroporin p7 and six non-structural (NS) proteins Velpatasvir is an inhibitor of the Hepatitis C Virus (HCV) Nonstructural protein 5A, which is required for viral RNA replication and assembly of HCV virions. The exact mechanism of this protein is unknown. Velpatasvir's mechanism of action is likely similar to other selective NS5A inhibitors which bind domain I of NS5A consisting of amino acids 33-202. NS5A inhibitors compete with RNA for binding at this site. It is also thought that NS5A inhibitors bind the target during its action in replication when the binding site is exposed. Viral RNA replication complexes localize to lipid raft-containing, detergent-resistant membranes created by the viral protein NS4B. For full viral replication and maturation, replication complexes need to be in close proximity to lipid droplets, which requires the protein nonstructural protein 5A. Without the lipid droplet due to inhibition of nonstructural protein 5A, full viral RNA replication is unable to occur. Envelope glycoproteins are acquired through budding into the endoplasmic reticulum lumen. The immature, non-infective virions are released via the cellular golgi apparatus.

Dasabuvir is a direct-acting antiviral agent used to treat specific hepatitis C virus (HCV) infections in combination with other antiviral agents, Ombitasvir, Paritaprevir, and Ritonavir. 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. The genome polyprotein is cleaved by host and viral proteases into 10 viral proteins. The nucleocapsid protein core and the two envelope proteins E1 and E2 form the N terminus of the polyprotein and are the structural components of HCV virions. The precursor also gives rise to the viroporin p7 and six non-structural (NS) proteins. Dasabuvir is an inhibitor of the Hepatitis C Virus (HCV) Nonstructural protein 5B, which is an RNA-dependent RNA polymerase. RNA polymerase is required for viral RNA replication and assembly of HCV virions. By binding to nonstructural protein 5B outside of the active site of the enzyme, dasabuvir induces a conformational change. Viral RNA replication complexes localize to lipid raft-containing, detergent-resistant membranes created by the viral protein NS4B. For full viral replication and maturation, nonstructural protein 5B is required so viral RNA replication cannot occur. Envelope glycoproteins are acquired through budding into the endoplasmic reticulum lumen. The immature, non-infective virions are released via the cellular golgi apparatus.

Pibrentasvir is a direct acting antiviral agent and Hepatitis C virus (HCV) nonstructural protein 5A inhibitor that targets the the viral RNA replication and viron assembly. In combination with Glecaprevir. 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. The genome polyprotein is cleaved by host and viral proteases into 10 viral proteins. The nucleocapsid protein core and the two envelope proteins E1 and E2 form the N terminus of the polyprotein and are the structural components of HCV virions. The precursor also gives rise to the viroporin p7 and six non-structural (NS) proteins. Pibrentasvir is an inhibitor of the Hepatitis C Virus (HCV) Nonstructural protein 5A, which is required for viral RNA replication and assembly of HCV virions. The exact mechanism of this protein is unknown. NS5A inhibitors compete with RNA for binding at this site. Viral RNA replication complexes localize to lipid raft-containing, detergent-resistant membranes created by the viral protein NS4B.ding site is exposed. For full viral replication and maturation, replication complexes need to be in close proximity to lipid droplets, which requires the protein nonstructural protein 5A. Without the lipid droplet due to inhibition of nonstructural protein 5A, full viral RNA replication is unable to occur. Envelope glycoproteins are acquired through budding into the endoplasmic reticulum lumen. The immature, non-infective virions are released via the cellular golgi apparatus.

Simeprevir is a direct-acting antiviral agent that inhibits HCV NS3/4A protease to treat chronic hepatitis C virus (HCV) infection in adults with HCV genotype 1 or 4. 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. Simeprevir accumulates in the liver after uptake into hepatocytes via solute carrier organic anion transporter family member 1B1. Simeprevir 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), simeprevir 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.

Glecaprevir is a direct acting antiviral agent and Hepatitis C virus (HCV) NS3/4A protease inhibitor used to treat Hepatitis C virus. Glecaprevir is taken in combination with Pibrentasvir as a useful therapy for patients who experienced therapeutic failure from other NS3/4A protease inhibitors. 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. Glecaprevir accumulates in the liver after uptake into hepatocytes via solute carrier organic anion transporter family member 1B1. Glecaprevir 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), glecaprevir 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.