Pathways

Interferon alfa-n1 is a purified and natural (n for natural) alpha interferon from humans. This drug stimulates the innate antiviral response. It is used in the treatment of venereal or genital warts caused by the Human Papilloma Virus (HPV). By binding to the type I interferon receptors (IFNAR1 and IFNAR2c), this drug activates the immune response through the Jak(Janus Kinase)-Stat pathway. In detail, when this interferon binds the IFNAR1 and IFNAR2c, they dimerize, activating two Jak tyrosine kinases. These transphosphorylate themselves and, thus, phosphorylate the receptors. When phosphorylated, the IFNAR1 and IFNAR2c can bind to Stat1 and Stat2 (signal transducers and activators of transcription. They will activate multiple immunomodulatory and antiviral proteins. This drug is available as an intramuscular or subcutaneous injection.

Peginterferon alfa-2b, also known as Pegintron or Sylatron, is a purified recombinant human interferon. It is used as part of combination therapy to treat chronic Hepatitis C caused by the Hepatitis C Virus (HCV). It is also used as an adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection. The mechanism of action is the inhibition of the viral replication in infected cells caused by the binding of the peginterferon to the human type 1 interferon receptors causing them to dimerize. This, in consequence, activates the JAK-STATS pathway which increases the expression of multiple genes involved in the innate antiviral response. Its immunomodulatory effects are the enhancement of the phagocytic activity, the activation of NK cells, the stimulation of cytotoxic T-lymphocytes, and the upregulation of the Th1 T-helper cell subset.

Interferon beta-1a is a recombinant form of the human interferon. It is used to slow disease progression and reduce the clinical symptoms of patients with relapsing multiple sclerosis (RMS). It can also be used for condyloma acuminatum. Interferon beta-1a binds to type 1 interferon receptors (IFNAR and IFNAR2c). This drug activates the dimerization of these receptors. This action activates the Jak tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the IFNAR and IFNAR2c. This receptor complex also phosphorylates STAT3 homodimers. The IFNAR complex phosphorylates STAT5 which binds with Crk-like protein (CRKL). This activates the transcription of gamma-activated sequence (GAS) elements, which activates an inflammatory response and immunoregulation. When phosphorylated, the receptors bind to Stat1 and Stat2, and together with the interferon regulatory factor (IRF9) they form the interferon-stimulated gene factor 3 (ISGF3). The ISGF3 translocates to the nucleus to initiate the transcription of the Interferon-sensitive response element (ISRE). This leads to an antiviral response, immunoregulation, antigen presentation, and checkpoint proteins. The ISRE genes also activate IFN-regulated genes. These along with lipopolysaccharides or foreign pathogens activates interferon Regulatory Factor 7 (IRF7). IRF7 is phosphorylated and bound with nuclear factor kappa B (NFKB). This causes the induction of type 1 INFs, which further activates the JAK/STAT pathway. IFNAR1 and IFNAR2 signal through TYK2 and JAK1 also trigger the activation of the NFKB pathway through phosphorylated STAT3, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and TNF receptor-associated factors (TRAFs). They act through IKKa and IKKb to drive NFKB induction of genes associated with survival signals, antigen processing and presentation, and proliferation.

Interferon alfacon-1 is a recombinant non-naturally occurring type 1 interferon. This drug is used as a treatment of hairy cell leukemia, malignant melanoma, and IDS-related Kaposi's sarcoma. Interferon alfacon-1 binds to type 1 interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak tyrosine kinases (Jak1 and Tyk2). This receptor complex also phosphorylates STAT3 homodimers. The IFNAR complex phosphorylates STAT5 which binds with Crk-like protein (CRKL). This activates the transcription of gamma-activated sequence (GAS) elements, which activates an inflammatory response and immunoregulation. The main pathway of IFNAR1 and IFNAR2 is through the phosphorylation of STAT1 and STAT2. Together with interferon regulatory factor (IRF9) they form the interferon-stimulated gene factor 3 (ISGF3). The ISGF3 translocates to the nucleus and initiates the transcription of the Interferon-sensitive response element (ISRE). This leads to an antiviral response, immunoregulation, antigen presentation, and checkpoint proteins. THE ISRE genes also activate IFN-regulated genes. These along with lipopolysaccharides or foreign pathogens activates interferon Regulatory Factor 7 (IRF7). IRF7 is phosphorylated and bound with nuclear factor kappa B (NFKB). This causes the induction of type 1 INFs, which further activates the pathway. IFNAR1 and IFNAR2 signal through TYK2 and JAK1 to also trigger the activation of the NFKB pathway through phosphorylated STAT3, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and TNF receptor-associated factors (TRAFs). They act through IKKa and IKKb to drive NFKB induction of genes associated with survival signals, antigen processing and presentation, and proliferation. This molecule is administered as an subcutaneous injection.

Interferon alpha 2a is arecombinant human interferon used to stimulate the antiviral response in Humans. It is used in the treatment of hepatitis B and C viruses (antiviral). In details, interferon a is a human leukacyte protein moiety reduced. This biotechnology drug is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. Interferon alpha binds to type 1 interferon receptors, also called IFNAR1 and IFNAR2c, which upon dimerization, activate two Jak tyrosine kinase (Jak1 and Tyk2). These transphosphorylate themselves and phosphoryle the receptors. This receptor complex also phosphorylates STAT3 homodimers. The IFNAR complex phorphoylates STAT5 which binds with Crk-like protein (CRKL). This activates the transcription of gamma activated sequence (GAS) elements, which activates an inflammatory response and immunoregulation. The main pathway of IFNAR1 and IFNAR2 is through the phosphorylation of STAT1 and STAT2. Together with interferon regulatory factor (IRF9) they form the interferon-stimulated gene factor 3 (ISGF3). The ISGF3 translocates to the nucleus and initiates the trascription of Interferon-sensitive response element (ISRE). This leads to an antiviral response, immunoregulation, antigen presentation, and checkpoint proteins. The ISRE genes also activate IFN regulated genes. These along with lipopolysaccharides or foreign pathogens activates interferon Regulatory Factor 7 (IRF7). IRF7 is phosphorylated and bound with nuclear factor kappa B (NFKB). This causes the induction of type 1 INFs, which further activates the pathway. IFNAR1 and IFNAR2 signal through TYK2 and JAK1 to also trigger the activation of the NFKB pathway through phosphorylated STAT3, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and TNF receptor-associated factors (TRAFs). They act through IKKa and IKKb to drive NFKB induction of genes associated with survival signals, antigen processing and presentation, and proliferation.

mTOR has significatant effect on the autophagy-lysosomal pathway

Interferon alfa-2b, also known as Intron A, is a recombinant human interferon used to treat hepatitis B and C infections. It can also treat genital warts, hairy cell leukemia, follicular lymphoma, malignant melanoma, and AIDs-related Kaposi's sarcoma. Interferon alpha binds to type 1 interferon receptors, called IFNAR1 and IFNAR2c, which upon dimerization activate two Jak tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. This receptor complex also phosphorylates STAT3 homodimers. The IFNAR complex phosphorylates STAT5 which binds with Crk-like protein (CRKL). This activates the transcription of gamma-activated sequence (GAS) elements, which activates an inflammatory response and immunoregulation. The main pathway of IFNAR1 and IFNAR2 is through the phosphorylation of STAT1 and STAT2. Together with interferon regulatory factor (IRF9) they form the interferon-stimulated gene factor 3 (ISGF3). The ISGF3 translocates to the nucleus and initiates the transcription of the Interferon-sensitive response element (ISRE). This leads to an antiviral response, immunoregulation, antigen presentation, and checkpoint proteins. The ISRE genes also activate IFN-regulated genes. These along with lipopolysaccharides or foreign pathogens activates interferon Regulatory Factor 7 (IRF7). IRF7 is phosphorylated and bound with nuclear factor kappa B (NFKB). This causes the induction of type 1 INFs, which further activates the pathway. IFNAR1 and IFNAR2 signal through TYK2 and JAK1 to also trigger the activation of the NFKB pathway through phosphorylated STAT3, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and TNF receptor-associated factors (TRAFs). They act through IKKa and IKKb to drive NFKB induction of genes associated with survival signals, antigen processing and presentation, and proliferation. This drug is administered as a solution that can be intralesional, intramuscular, intravenous, or subcutaneous.

Ansuvimab (formerly mAb114) is a monoclonal IgG1 antibody derived from a survivor of the 1995 kikwit EBOV (Ebola virus) outbreak. It is directed against the GP1,2 surface glycoprotein of Zaire ebolavirus .It is used for the treatment of Zaire ebolavirus infection in adult and pediatric patients. This drug has been approved by the FDA in 2020. The DP1,2 glycoproteins of EBOV are involved in the the host cell entry and the subsequent viral espape into the cytoplasm. Usually, those glycoproteins bind to various host receptors (lectins, asialoglycoprotein receptor, TIM1), but with the drug, they are blocked. Ansuvimab binds over a region encompassing both the glycan cap and GP1 core, although the glycan cap isnot important in the binding. Also, studies have shown that the GP1 core is important for the GPCL interaction with NPC1 and thus this drug blocks NPC1-GP interactions (endolysosome escape). The drug protect against the entry of the virus in the host cells. Ansuvimab is available as an intravenous injection.

Tecovirimat (Tpoxx) is an antiviral used in the treatment of smallpox, monkeypox and cowpox. In fact, this drug is effective against all orthopoxviruses, including vaccinia, cowpox, ectromelia, rabbitpox, monkeypox and variola virus (smallpox). Tecovirimat was approved by the FDA in July 2018. Tecovirimal is an inhibitor of the P37 protein (VP37 envelope-wrapping protein)) of the orthopoxvirus. This protein is essential to form the wrapping complex of mature virions with late endosomal membranes by interacting with proteins such as Rab9 GTPase and TIP47.. The P37 protein is encoded by a highly conserved gene in all members of the orthopoxvirus genus. When Tecovirimat binds P37, this protein can not interact with the Rab9 GTPase and TIP47, which are components of late endosome-derived transport vesicles. In consequence, there is no formation of the wrapping complex for enveloped virions. This drug is available as an oral tablet and an intravenous formulation.

Zanamivir, also known as Relenza, is an inhibitor of the viral neuraminidase protein. This antiviral is used to treat and prevent influenza A and B infections. By interacting with the neuraminidase, Zabamivir renders the influenza virus unable to escape its host cell. Neuraminidases are essential for the cleaving of the terminal sialic acids on the glycosylated HA during the virus budding to facilitate its release. In consequence, the virus will not be able to infect other cells. This molecule is available as an intravenous solution or as a powder for inhalation.