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HCV is a small 50nm, enveloped, single-stranded, positive sense RNAvirus in the family Flaviviridae.
HCV has a high rate of replication with approximately one trillion particles produced each day in an infected individual. Due to lack of proofreading by the HCV RNA polymerase, the HCV has an exceptionally high mutation rate, a factor that may help it elude the host's immune response. Hepatitis C virus is classified into six genotypes(1-6) with several subtypes within each genotype. The preponderance and distribution of HCV genotypes varies globally. Genotype is clinically important in determining potential response to interferon-based therapy and the required duration of such therapy. Genotypes 1 and 4 are less responsive to interferon-based treatment than are the other genotypes (2, 3, 5 and 6).

Human norovirus is classified into two groups, group 1& group 2. Norwalk virus is the species which belongs to group 1 and was discovered in 1968 at Ohio. Norovirus is a familiar virus which causes human gastroenteritis with the following symptoms vomiting, diarrhea and sickness. CDC report revealed that there are 19-21 million Americans infected by Nororvirus annually with 800 deaths, 1 in 15 people with infection. Around the world, this virus affects about 267 million people and causes over 200,000 deaths each year; these losses are mostly in less developed countries and in the very young, elderly and immuno-suppressed population, though, most cases are self-limited with a full recovery within just a few days.Norovirus is extremely contagious and can spread from human to human through infected food, water or contaminated surfaces. The outbreaks usually occur from November-April, while the peak is in January. Norovirus is a positive sense RNA virus with 7.5 kb nucleotides, encoding a major structural protein VP1 with 50-55kDa. The full length of VP1 capsid comprises the internal N-terminal, Hinge, shell (S) and protruding (P) domains. P domain from 225 to 520 forms P1- P2-P1 structure. Moreover, P domain has a receptor binding region which recognizes human histo-blood group antigens (HBGAs). P domain expressed in bacteria can spontaneously form a P dime as well as a P particle aggregated by 12 P dimmers. P particle displays an increased binding activity to HBGAs higher than virus-like particle (VLP) formed by the full-length capsid. For norovirus vaccine development, we consider P domain as a good candidate.

Mycoplasma pneumonia is part of the atypical pneumonia subtype which is caused by the bacteria M. pneumoniae. Mycoplasma pneumonia affects individuals younger than 40. It makes up 15 - 50% of all pneumonia cases in adults and especially in school-aged children. People at great risk for mycoplasma pneumonia comprise of those living or working in busy areas such as schools and homeless shelters, although many people who contract mycoplasma pneumonia have no identifiable risk factor. P1, P30, and P116 of mycoplasma pneumonia membrane proteins have been recognized as adhensive factors, P1 is considered as a main adhension protein of the organism colonization.

Prothrombin Complex Concentrate (PCC) is a combination of several blood clotting factors II, VII, IX and X. PCC is used in the treatment of the congenital bleeding disorders associated with Factors II, VII, IX, and X deficiencies. PCC reverses the effect of warfarin (a coumarin anti-coagulant) and is used in cases of significant bleeding in patients with a coagulopathy, for example, gastrointestinal haemorrhage or intracranial haemorrhage. The PCC is also extensively used in treating acquired coagulation abnormalities secondary to vitamin K deficiency, warfarin ingestion, and various types of liver disease.
Hepatitis, anaphylaxis and thrombosis have been reported as complications of prothrombin complex concentrates administration.

Tyrosine 3-monooxygenase (Th), is a rate-limiting enzyme in catecholamine synthesis. Th utilizes tetrahydrobiopterin as well as molecular oxygen to convert tyrosine to DOPA. Th regulates dopamine (DA) neurotransmission at the biosynthesis and reuptake steps. Th takes a vital part in the physiology of adrenergic neurons. Furthermore, Th effects overexpression in lymphocytes on the differentiation as well as function of T helper cells.

Mouse MIP-1 gamma is 75% identical in its amino acid compostion as compared to the rat specie. MIP-1 gamma is a CC chemokine localized in murine blood and a widespread range of murine tissues, without having an identified human homolog. MIP-1 gamma signals through the CCR1 receptor. MIP-1 gamma chemoattracts neutrophils and also inhibits colony formation of bone marrow myeloid immature progenitors. MIP-1 gamma has six cysteines including the four highly conserved cysteine residues present in CC chemokines.

Since April 2012, cases of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) have been identified in various countries. Coronaviruses are the cause of the common cold, SARS (severe acute respiratory syndrome) and other severe illnesses with high mortality rates, all are classified into coronavirus family. MERS-CoV is a new type of SARS found in the coronavirus family causing severe pneumonia with sudden and serious respiratory illness with high mortality rates as well. Since January 27th 2015, the WHO has reported 956 human cases, including 351 deaths. More cases of the new coronavirus strain are expected. Like in other coronaviruses, large surface spike glycoprotein is a central structural protein of this virus; it is located above the virion surface to bind and enter into the target cell. Spike protein has 2 domains- S1 and S2. The S1 domain is responsible for cellular tropism and interaction with target cell, while the S2 domain is responsible for membrane fusion. The C-terminal of S1 domain contains a receptor binding domain, and is also a potential target for vaccine development and an antigen for diagnosis.

Since April 2012, cases of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) have been identified in various countries. Coronaviruses are the cause of the common cold, SARS (severe acute respiratory syndrome) and other severe illnesses with high mortality rates, all are classified into coronavirus family. MERS-CoV is a new type of SARS found in the coronavirus family causing severe pneumonia with sudden and serious respiratory illness with high mortality rates as well. Since January 27th 2015, the WHO has reported 956 human cases, including 351 deaths. More cases of the new coronavirus strain are expected. Like in other coronaviruses, large surface spike glycoprotein is a central structural protein of this virus; it is located above the virion surface to bind and enter into the target cell. Spike protein has 2 domains- S1 and S2. The S1 domain is responsible for cellular tropism and interaction with target cell, while the S2 domain is responsible for membrane fusion. The C-terminal of S1 domain contains a receptor binding domain, and is also a potential target for vaccine development and an antigen for diagnosis.

HCV is a small 50nm, enveloped, single-stranded, positive sense RNAvirus in the family Flaviviridae.
HCV has a high rate of replication with approximately one trillion particles produced each day in an infected individual. Due to lack of proofreading by the HCV RNA polymerase, the HCV has an exceptionally high mutation rate, a factor that may help it elude the host's immune response. Hepatitis C virus is classified into six genotypes(1-6) with several subtypes within each genotype. The preponderance and distribution of HCV genotypes varies globally. Genotype is clinically important in determining potential response to interferon-based therapy and the required duration of such therapy. Genotypes 1 and 4 are less responsive to interferon-based treatment than are the other genotypes (2, 3, 5 and 6).

NAPA is part of the SNAP (Soluble NSF Attachment Protein) family. SNAPs, acting together with SNAREs (SNAP receptors) and the N-ethylmaleimide-sensitive fusion protein (NSF), are necessary for the fusion of transport vesicles to their objective membranes in synaptic transmission, intra-Golgi transport, endosome-to-endosome fusion and transcytotic vesicles-to-plasma membrane transport. NAPA is in charge of the binding of NSF and therefore the formation of a 20S fusion particle.

TRAF2 protein is related with transduce signals from members of the TNFR superfamily. TRAF2 is located in the cytoplasm binds to TRAF1, TRAF2, or TRAF3, thus inhibiting TRAF function by sequestering the TRAFs in a suppressed state in the cytoplasm. Overexpression of TANK inhibits TRAF2-mediated NF-Kappa-B activation signaled by CD40 and both TNF receptors and inhibits LMP1-mediated NF-kappa-B activation by blocking the association of TRAF2 with LMP1. TRAF2 is necessary for the cellular response to TNF-alpha by connecting upstream signalling molecules to the IKKs and p65.

NCS1 is part of the neuronal calcium sensor gene family, which encode calcium-binding proteins expressed primarily in neurons. NCS1 regulates G protein-coupled receptor phosphorylation in a calcium-dependent manner and can substitute for calmodulin. NCS1 is related with secretory granules and modulates synaptic transmission and synaptic plasticity. NCS1 regulates GRK1 and substitutes for calmodulin. NCS1 stimulates PI4KB kinase activity and participates in long-term synaptic plasticity through its interaction with PICK1. NCS1 takes part in neuron differentiation through inhibition of the activity of N-type voltage-gated calcium channel.

NME2 takes an important part in the synthesis of nucleoside triphosphates other than ATP. NME2 negatively controls Rho activity by interacting with AKAP13/LBC. NME2 acts as a transcriptional activator of the MYC gene. NME2 binds DNA non-specifically. NME2 is a heterodimeric enzyme functioning as a nucleoside diphosphate kinase. NME1 and NME2 contain 152 amino acids, A and B polypeptide chains of the NM23 enzyme, respectively. NME2 is identical to the beta subunit of human erythrocyte NDP kinase. NDP kinases participate in the synthesis of nucleoside triphosphates, and NM23 is involved in the regulation of signal transduction by complexing with G proteins, causing activation/inactivation of developmental pathways.

Matrix metalloproteinase-7 (MMP-7) also known as matrilysin and PUMP (EC 3.4.24.23) cleaves a number of substrates including collagen types IV and X, elastin, fibronectin, gelatin, laminin and proteoglycans. MMP-7 is closely related to the stromelysin family members but is encoded by a different gene. MMP-7 is the smallest of all the MMPs consisting of a pro-peptide domain and a catalytic domain. It lacks the hemopexin-like domain common to other members of the MMPs. MMP-7 is secreted as a 28 kDa proenzyme and can be activated in vitro by organomercurials and trypsin and in vivo by MMP-3 to a 18 kDa active MMP-7 enzyme. Once activated, MMP-7 can activate pro-MMP-1 and pro-MMP-9 but not pro-MMP-2. MMP-7 is widely expressed having been reported in elevated levels in cycling endometrium as well as in colorectal cancers and adenomas, hepatocellular carcinomas, rectal carcinomas, and approximately 50% of gliomas.

Tyrosyl-DNA Phosphodiesterase 2 (TDP2), belongs to the CCR4/nocturin family of divalent cation-dependent phosphodiesterases.TDP2 associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor associated factors (TRAFs), and inhibits nuclear factor-kappa-B activation. TDP2 is characterized by similar sequence and structure as APE1 endonuclease, which participates in DNA repair and the activation of transcription factors.

Paraoxonase-1 or PON1 is part of the paraoxonase group of proteins. PON1 is an enzyme, responsible to the toxic metabolites of a different of organophosphorus insecticides hydrolyzation. Furthermore, PON1 is a dominant anti-atherosclerotic part of HDL. The enzyme needs PPAR-gamma for activation, leading to synthesis and release of paraoxonase 1 from the liver tissue, resulting in atherosclerosis reduction. PON1 has many qualities for atheroprotective through inflammatory lipid peroxides metabolism. This enzyme can hydrolyze a large number of substrates, for example cyclic carbonates, lactones, nerve gases etc.

Midkine (MK) is the product of a retinoic acid responsive gene. It contains 121 amino acid residues including 10 conserved cysteine residues, all of which appear to be disulphide linked.
Midkine is expressed during embryogenesis, showing an expression pattern that suggests functions in neurogenesis, cell migration, secondary organogenetic induction, and mesoderm-epithelial interaction.
The widespread downregulation of MK in the adult human is reverted in a number of cancers, in which polypeptides are able to act as both transforming growth factors and promoters of angiogenesis.
Midkine (MK), induces chemotaxis of human neutrophils and was found to trigger mobilization of intracellular calcium of these cells.
Midkine induces histamine release from rat peritoneal mast cells with a rapid response in a dose dependent manner.
Midkine is also a potent stimulator of collagen and glycosaminoglycan synthesis.

Neuroglobin, 151 amino acid residue protein, mainly expressed in vertebrate brain and retina, is a recently identified member of the globin superfamily. Augmenting O (2) supply, neuroglobin promotes survival of neurons upon hypoxic injury, potentially limiting brain damage. Moreover, neuroglobin may be a novel oxidative stress-responsive sensor for signal transduction in the brain. Neuroglobin expression is increased by neuronal hypoxia in vitro and focal cerebral ischemia in vivo, and neuronal survival after hypoxia is reduced by inhibiting neuroglobin expression with an antisense oligodeoxynucleotide and enhanced by neuroglobin overexpression.

Elongin B (Elob) is a subunit of the transcription factor B (SIII) complex. SIII complex is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. The SIII complex comprised of a transcriptionally active subunit (A) and 2 regulatory subunits (B and C). Subunit A is transcriptionally active and its transcription activity is enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C. The von Hippel-Lindau tumor suppressor protein binds to elongin B and C and inhibits transcription elongation.

TNFRSF13B (TACI) is a transmembrane receptor protein found predominantly on the surface of B cells (a significant part of the immune system). TACI was at first discovered owing to its ability to interact with calcium-modulator and cyclophilin ligand (CAML). Later on, it was found that TACI plays a key role in humoral immunity by interacting with two members of the TNF family. Also, TACI controls T cell-independent B cell antibody responses, isotype switching, and B cell homeostasis.

Potassium Channel Tetramerisation Domain Containing 11 (KCTD11) is a 232 amino acid regulator of neuronal differentiation which induces growth arrest, apoptosis and the expression of p27 (cyclin-dependent kinase inhibitor). KCTD11 is expressed most highly in cerebellum. KCTD11 functions as an antagonist of the Hedgehog pathway and activator of the caspase cascade and among its related super-pathways are Melatonin Signaling and Activation of cAMP-Dependent PKA.

Tumor necrosis factor is a cytokine involved in systemic inflammation and is a member of a group of cytokines that all stimulate the acute phase reaction. TNF is mainly secreted by macrophages.
TNF causes apoptotic cell death, cellular proliferation, differentiation, inflammation, tumorigenesis and viral replication, TNF is also involved in lipid metabolism, and coagulation. TNF's primary role is in the regulation of immune cells.
Dysregulation and, in particular, overproduction of TNF have been implicated in a variety of human diseases- autoimmune diseases, insulin resistance, and cancer.

TNFR1 belongs to the TNF-receptor superfamily. TNFR1 is a receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha.
There are 2 types of soluble TNF receptors: sTNFR-I and sTNFR-II, which act to neutralize the biological activities of TNF alpha and TNF beta. The levels of these soluble receptors seem to increase as a result of shedding of the extracellular domains of the membrane bound receptors. TNF-a, TNFR1 and TNFR2 have roles in cellular differentiation. TNFR1 and TNFR2 function in cell type-specific renal injury.
TNFR1 is capable of signaling both cell survival and apoptosis. TNFR1-induced apoptosis requires 2 sequential signaling complexes. TNFR1 is capable of activating NF-kappaB, mediate apoptosis, and function as a regulator of inflammation. Oxidative stress promotes TNFR1 and TNFR2 self-interaction, ligand-independent and enhanced ligand-dependent TNF signaling. TNFR1 contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase. Human TNFR1 has a major region which controls cell surface expression. High levels of soluble TNF receptors are found in the amniotic fluid of pregnant women.
Germline mutations of the extracellular domains of TNFR1 are linked to the autosomal dominant periodic fever syndrome. The impaired receptor clearance is believed to be a mechanism of the disease. Familial hibernian fever (FHF) is caused by defects in TNFRSF1A gene.

TNFR2 belongs to the TNF-receptor superfamily. TNFR2 is receptor with high affinity for TNFSF2/TNF-alpha and approximately 5-fold lower affinity for homotrimeric TNFSF1/lymphotoxin-alpha. TNFR2 mediates the majority of the metabolic effects of TNF-alpha. In addition, knockout studies in mice propose a role for TNFR2 in protecting neurons from apoptosis by stimulating antioxidative pathways. TNFR2 expression might have a significant role in the angiogenesis, tumor cell proliferation and metastasis of Invasive micropapillary carcinoma of the breast.
There are 2 types of soluble TNF receptors: sTNFR-I and sTNFR-II, which act to neutralize the biological activities of TNF alpha and TNF beta. The levels of these soluble receptors seem to increase as a result of shedding of the extracellular domains of the membrane bound receptors. High levels of soluble TNF receptors are found in the amniotic fluid of pregnant women. TNFR2 and TNFR1 form a heterocomplex which mediates the recruitment of 2 anti-apoptotic proteins, c-IAP1 and c-IAP2, which possess E3 ubiquitin ligase activity. IAPs’ function in TNF-receptor signaling is unknown; nevertheless, c-IAP1 is believed to potentiate TNF-induced apoptosis by the ubiquitination and degradation of TNF-receptor-associated factor 2, which mediates anti-apoptotic signals. Oxidative stress promotes TNFR1 and TNFR2 self-interaction, ligand-independent and enhanced ligand-dependent TNF signaling. TNF-a, TNFR1 and TNFR2 have roles in cellular differentiation. TNFR1 and TNFR2 function in cell type-specific renal injury.