Hepatitis C virus HCV human hepatitis C virus
77-460: The Hepatitis C virus internal ribosome entry site , or HCV IRES , is an RNA structure within the 5'UTR of the HCV genome that mediates cap-independent translation initiation. Protein translation of most eukaryotic mRNAs occurs by a cap-dependent mechanism and requires association of Met- tRNA i , several eukaryotic initiation factors , and GTP with the 40S ribosomal subunit, recruitment to
154-403: A linear combination of atomic orbitals is performed first, followed by filling of the resulting molecular orbitals with electrons. The two approaches are regarded as complementary, and each provides its own insights into the problem of chemical bonding. As valence bond theory builds the molecular wavefunction out of localized bonds, it is more suited for the calculation of bond energies and
231-452: A lipid membrane envelope that is 55 to 65 nm in diameter. Two viral envelope glycoproteins , E1 and E2 , are embedded in the lipid envelope. They take part in viral attachment and entry into the cell. Within the envelope is an icosahedral core that is 33 to 40 nm in diameter. Inside the core is the RNA material of the virus. E1 and E2 are covalently bonded when embedded in
308-427: A complex, priming them for later HCV infection processes. As the immune system is triggered, macrophages increase the amount of TNF-α around the hepatocytes which are being infected. This triggers the migration of occludin, which is another tight-junction complex, to the basolateral membrane. The HCV particle is ready to enter the cell. These interactions lead to the endocytosis of the viral particle. This process
385-559: A frameshift may occur in the Core region to produce an alternate reading frame protein (ARFP). HCV encodes two proteases, the NS2 cysteine autoprotease and the NS3-4A serine protease. The NS proteins then recruit the viral genome into an RNA replication complex, which is associated with rearranged cytoplasmic membranes. RNA replication takes place via the viral RNA-dependent RNA polymerase NS5B, which produces
462-442: A full (or closed) outer electron shell. In the diagram of methane shown here, the carbon atom has a valence of four and is, therefore, surrounded by eight electrons (the octet rule ), four from the carbon itself and four from the hydrogens bonded to it. Each hydrogen has a valence of one and is surrounded by two electrons (a duet rule) – its own one electron plus one from the carbon. The numbers of electrons correspond to full shells in
539-495: A lesser degree, etc.; thus a "co-valent bond", in essence, means that the atoms share " valence ", such as is discussed in valence bond theory . In the molecule H 2 , the hydrogen atoms share the two electrons via covalent bonding. Covalency is greatest between atoms of similar electronegativities . Thus, covalent bonding does not necessarily require that the two atoms be of the same elements, only that they be of comparable electronegativity. Covalent bonding that entails
616-439: A manner that AUG initiator codon is positioned in the ribosomal P-site, thus no ribosomal scanning is required. Consequently scanning factors eIF1 and eIF1A are dispensable for the HCV translation, as are components of the eIF4F complex ( eIF4A , eIF4E , and eIF4G ) and eIF4B , which are generally required for mRNA binding and unwinding of 5'UTR . Initiator tRNA is delivered either by eIF2 or, in stress conditions when eIF2
693-458: A mixture of atoms and ions. On the other hand, simple molecular orbital theory correctly predicts Hückel's rule of aromaticity, while simple valence bond theory incorrectly predicts that cyclobutadiene has larger resonance energy than benzene. Although the wavefunctions generated by both theories at the qualitative level do not agree and do not match the stabilization energy by experiment, they can be corrected by configuration interaction . This
770-473: A negative strand RNA intermediate. The negative strand RNA then serves as a template for the production of new positive strand viral genomes. Nascent genomes can then be translated, further replicated or packaged within new virus particles. The virus replicates on intracellular lipid membranes. The endoplasmic reticulum in particular is deformed into uniquely shaped membrane structures termed 'membranous webs'. These structures can be induced by sole expression of
847-464: A poor response to treatment has been reported. In vitro work has shown that vitamin D may be able to reduce viral replication. While this work looks promising the results of clinical trials are pending. However, it has been proposed that vitamin D supplementation is important in addition to standard treatment, in order to enhance treatment response. Naringenin , a flavonoid found in grapefruit and other fruits and herbs, has been shown to block
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#1732895537984924-508: A regular hexagon exhibiting a greater stabilization than the hypothetical 1,3,5-cyclohexatriene. In the case of heterocyclic aromatics and substituted benzenes , the electronegativity differences between different parts of the ring may dominate the chemical behavior of aromatic ring bonds, which otherwise are equivalent. Certain molecules such as xenon difluoride and sulfur hexafluoride have higher co-ordination numbers than would be possible due to strictly covalent bonding according to
1001-420: A single Lewis structure is insufficient to explain the electron configuration in a molecule and its resulting experimentally-determined properties, hence a superposition of structures is needed. The same two atoms in such molecules can be bonded differently in different Lewis structures (a single bond in one, a double bond in another, or even none at all), resulting in a non-integer bond order . The nitrate ion
1078-478: A single open reading frame that is 9,600 nucleotide bases long. This single open reading frame is translated to produce a single protein product, which is then further processed to produce smaller active proteins. This is why on publicly available databases, such as the European Bioinformatics Institute , the viral proteome only consists of 2 proteins. At the 5′ and 3′ ends of the RNA are
1155-488: Is aided by clathrin proteins. Once inside an early endosome, the endosome and the viral envelope fuse and the RNA is allowed into the cytoplasm. HCV takes over portions of the intracellular machinery to replicate. The HCV genome is translated to produce a single protein of around 3,011 amino acids. The polyprotein is then proteolytically processed by viral and cellular proteases to produce three structural (virion-associated) and seven nonstructural (NS) proteins. Alternatively,
1232-412: Is also current experimental research on non drug related therapies. Oxymatrine , for example, is a root extract found in the continent of Asia that has been reported to have antiviral activity against HCV in cell cultures and animal studies. Small and promising human trials have shown beneficial results and no serious side effects, but they were too small to generalize conclusions. On October 5, 2020, it
1309-590: Is also intra-hospital ( nosocomial ) transmission, when practices of hygiene and sterilization are not correctly followed in the clinic. A number of cultural or ritual practices have been proposed as a potential historical mode of spread for HCV, including circumcision, genital mutilation, ritual scarification, traditional tattooing and acupuncture. It has also been argued that given the extremely prolonged periods of persistence of HCV in humans, even very low and undetectable rates of mechanical transmission via biting insects may be sufficient to maintain endemic infection in
1386-461: Is an evolutionary adaptation of HCV over many centuries to these populations’ immunogenetic responses. Infection with one genotype does not confer immunity against others, and concurrent infection with two strains is possible. In most of these cases, one of the strains outcompetes the other in a short time. This finding may be useful in treatment, in replacing strains non-responsive to medication with others easier to treat. When two viruses infect
1463-591: Is cleaved by a metal-dependent autocatalytic proteinase encoded within NS2 and the N-terminus of NS3. The remaining cleavages downstream from this site are catalysed by a serine protease also contained within the N-terminal region of NS3. An 11th protein has also been described. This protein is encoded by a +1 frameshift in the capsid gene. It appears to be antigenic but its function is unknown. Replication of HCV involves several steps. The virus replicates mainly in
1540-423: Is defined as where g | n , l , m l , m s ⟩ A ( E ) {\displaystyle g_{|n,l,m_{l},m_{s}\rangle }^{\mathrm {A} }(E)} is the contribution of the atomic orbital | n , l , m l , m s ⟩ {\displaystyle |n,l,m_{l},m_{s}\rangle } of
1617-493: Is denoted as the covalency of the A−B bond, which is specified in the same units of the energy E {\displaystyle E} . An analogous effect to covalent binding is believed to occur in some nuclear systems, with the difference that the shared fermions are quarks rather than electrons. High energy proton -proton scattering cross-section indicates that quark interchange of either u or d quarks
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#17328955379841694-468: Is done by combining the valence bond covalent function with the functions describing all possible ionic structures or by combining the molecular orbital ground state function with the functions describing all possible excited states using unoccupied orbitals. It can then be seen that the simple molecular orbital approach overestimates the weight of the ionic structures while the simple valence bond approach neglects them. This can also be described as saying that
1771-485: Is inactivated, by eIF2A , eIF2D , or possibly eIF5B , a homologue of prokaryotic IF2 protein. Hepatitis C virus The hepatitis C virus ( HCV ) is a small (55–65 nm in size), enveloped , positive-sense single-stranded RNA virus of the family Flaviviridae . The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer ( hepatocellular carcinoma , abbreviated HCC) and lymphomas in humans. The hepatitis C virus belongs to
1848-409: Is integrated within a predicted pseudoknot . The conformation of this core domain constrains the open reading frame's orientation for positioning on the 40S ribosomal subunit . The large pre-protein is later cleaved by cellular and viral proteases into the 10 smaller proteins that allow viral replication within the host cell, or assemble into the mature viral particles. Structural proteins made by
1925-625: Is known as covalent bonding. For many molecules , the sharing of electrons allows each atom to attain the equivalent of a full valence shell, corresponding to a stable electronic configuration. In organic chemistry, covalent bonding is much more common than ionic bonding . Covalent bonding also includes many kinds of interactions, including σ-bonding , π-bonding , metal-to-metal bonding , agostic interactions , bent bonds , three-center two-electron bonds and three-center four-electron bonds . The term covalent bond dates from 1939. The prefix co- means jointly, associated in action, partnered to
2002-625: Is normally utilized to bud vesicles out of the cell. The only limitation to this hypothesis is that the pathway is normally used for cellular budding , and it is not known how HCV would commandeer the ESCRT pathway for use with the endoplasmic reticulum. Based on genetic differences between HCV isolates, the hepatitis C virus species is classified into six genotypes (1–6) with several subtypes within each genotype (represented by lowercase letters). Subtypes are further broken down into quasispecies based on their genetic diversity. Genotypes differ by 30–35% of
2079-408: Is one such example with three equivalent structures. The bond between the nitrogen and each oxygen is a double bond in one structure and a single bond in the other two, so that the average bond order for each N–O interaction is 2 + 1 + 1 / 3 = 4 / 3 . [REDACTED] In organic chemistry , when a molecule with a planar ring obeys Hückel's rule , where
2156-466: Is proposed to be caused by a single-nucleotide polymorphism (SNP) on chromosome 19 of the human genome that is predictive of treatment success. HCV genotypes 1 and 4 have been distributed endemically in overlapping areas of West and Central Africa, infecting for centuries human populations carrying the genetic polymorphism in question. This has prompted scientists to suggest that the protracted persistence of HCV genotypes 1 and 4 in people of African origin
2233-553: Is thought to have its origin in South East Asia. These dates from these various countries suggests that this virus may have evolved in South East Asia and was spread to West Africa by traders from Western Europe. It was later introduced into Japan once that country's self-imposed isolation was lifted. Once introduced to a country its spread has been influenced by many local factors including blood transfusions, vaccination programmes, intravenous drug use and treatment regimes. Given
2310-599: The 5' cap , and scanning along the 5' UTR to reach to start codon. In contrast, translation of hepatitis C virus (HCV) mRNA is initiated by a different mechanism from the usual 5' cap-binding model. This alternate mechanism relies on the direct binding of the 40S ribosomal subunit by the internal ribosome entry site (IRES) in the 5' UTR of HCV RNA. The HCV IRES adopts a complex structure, and may differ significantly from IRES elements identified in picornaviruses . A small number of eukaryotic mRNAs has been shown to be translated by internal ribosome entry. Nucleotides 1–40 of
2387-400: The hepatocytes of the liver , where it is estimated that daily each infected cell produces approximately fifty virions (virus particles) with a calculated total of one trillion virions generated. The virus may also replicate in peripheral blood mononuclear cells , potentially accounting for the high levels of immunological disorders found in chronically infected HCV patients. In the liver,
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2464-615: The octet rule . This is explained by the three-center four-electron bond ("3c–4e") model which interprets the molecular wavefunction in terms of non-bonding highest occupied molecular orbitals in molecular orbital theory and resonance of sigma bonds in valence bond theory . In three-center two-electron bonds ("3c–2e") three atoms share two electrons in bonding. This type of bonding occurs in boron hydrides such as diborane (B 2 H 6 ), which are often described as electron deficient because there are not enough valence electrons to form localized (2-centre 2-electron) bonds joining all
2541-450: The untranslated regions (UTR), that are not translated into proteins but are important to translation and replication of the viral RNA. The 5′ UTR has a ribosome binding site or internal ribosome entry site (IRES) that initiates the translation of a very long protein containing about 3,000 amino acids. The core domain of the HCV IRES contains a four-way helical Holliday junction that
2618-446: The HCV mRNA are thought not to contribute to translation, and are rather required for genomic RNA replication. The remainder of the HCV 5'-UTR consists of three domains, namely domains II-IV (domain I is located on the 5'-end of the mRNA). HCV IRES independently binds two components of eukaryotic translation initiation machinery, the multiprotein initiation factor eIF3 and 40S small ribosomal subunit. Moreover, it binds 40S in such
2695-438: The HCV particles are brought into the hepatic sinusoids by blood flow. These sinusoids neighbor hepatocyte cells. HCV is able to pass through the endothelium of the sinusoids and make its way to the basolateral surface of the hepatocyte cells. HCV has a wide variety of genotypes and mutates rapidly due to a high error rate on the part of the virus' RNA-dependent RNA polymerase . The mutation rate produces so many variants of
2772-459: The ability to form three or four electron pair bonds, often form such large macromolecular structures. Bonds with one or three electrons can be found in radical species, which have an odd number of electrons. The simplest example of a 1-electron bond is found in the dihydrogen cation , H 2 . One-electron bonds often have about half the bond energy of a 2-electron bond, and are therefore called "half bonds". However, there are exceptions: in
2849-513: The assembly of intracellular infectious viral particles without affecting intracellular levels of the viral RNA or protein. Other agents that are under investigation include nucleoside and nucleotide analogue inhibitors and non-nucleoside inhibitors of the RNA-dependent RNA polymerase, inhibitors of NSP5A, and host-targeted compounds such as cyclophilin inhibitors and silibinin . Sofosbuvir for use against chronic hepatitis C infection
2926-432: The atom A to the total electronic density of states g ( E ) {\displaystyle g(E)} of the solid where the outer sum runs over all atoms A of the unit cell. The energy window [ E 0 , E 1 ] {\displaystyle [E_{0},E_{1}]} is chosen in such a way that it encompasses all of the relevant bands participating in
3003-986: The atoms together, but generally, there are negligible forces of attraction between molecules. Such covalent substances are usually gases, for example, HCl , SO 2 , CO 2 , and CH 4 . In molecular structures, there are weak forces of attraction. Such covalent substances are low-boiling-temperature liquids (such as ethanol ), and low-melting-temperature solids (such as iodine and solid CO 2 ). Macromolecular structures have large numbers of atoms linked by covalent bonds in chains, including synthetic polymers such as polyethylene and nylon , and biopolymers such as proteins and starch . Network covalent structures (or giant covalent structures) contain large numbers of atoms linked in sheets (such as graphite ), or 3-dimensional structures (such as diamond and quartz ). These substances have high melting and boiling points, are frequently brittle, and tend to have high electrical resistivity . Elements that have high electronegativity , and
3080-400: The atoms. However the more modern description using 3c–2e bonds does provide enough bonding orbitals to connect all the atoms, so that the molecules can instead be classified as electron-precise. Each such bond (2 per molecule in diborane) contains a pair of electrons which connect the boron atoms to each other in a banana shape, with a proton (the nucleus of a hydrogen atom) in the middle of
3157-737: The bond covalency can be provided in this way. The mass center c m ( n , l , m l , m s ) {\displaystyle cm(n,l,m_{l},m_{s})} of an atomic orbital | n , l , m l , m s ⟩ , {\displaystyle |n,l,m_{l},m_{s}\rangle ,} with quantum numbers n , {\displaystyle n,} l , {\displaystyle l,} m l , {\displaystyle m_{l},} m s , {\displaystyle m_{s},} for atom A
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3234-430: The bond, sharing electrons with both boron atoms. In certain cluster compounds , so-called four-center two-electron bonds also have been postulated. After the development of quantum mechanics, two basic theories were proposed to provide a quantum description of chemical bonding: valence bond (VB) theory and molecular orbital (MO) theory . A more recent quantum description is given in terms of atomic contributions to
3311-438: The bond. If the range to select is unclear, it can be identified in practice by examining the molecular orbitals that describe the electron density along with the considered bond. The relative position C n A l A , n B l B {\displaystyle C_{n_{\mathrm {A} }l_{\mathrm {A} },n_{\mathrm {B} }l_{\mathrm {B} }}} of
3388-440: The case of dilithium , the bond is actually stronger for the 1-electron Li 2 than for the 2-electron Li 2 . This exception can be explained in terms of hybridization and inner-shell effects. The simplest example of three-electron bonding can be found in the helium dimer cation, He 2 . It is considered a "half bond" because it consists of only one shared electron (rather than two); in molecular orbital terms,
3465-587: The connected atoms which determines the chemical polarity of the bond. Two atoms with equal electronegativity will make nonpolar covalent bonds such as H–H. An unequal relationship creates a polar covalent bond such as with H−Cl. However polarity also requires geometric asymmetry , or else dipoles may cancel out, resulting in a non-polar molecule. There are several types of structures for covalent substances, including individual molecules, molecular structures , macromolecular structures and giant covalent structures. Individual molecules have strong bonds that hold
3542-605: The contributions of the magnetic and spin quantum numbers are summed. According to this definition, the relative position of the A levels with respect to the B levels is where, for simplicity, we may omit the dependence from the principal quantum number n {\displaystyle n} in the notation referring to C n A l A , n B l B . {\displaystyle C_{n_{\mathrm {A} }l_{\mathrm {A} },n_{\mathrm {B} }l_{\mathrm {B} }}.} In this formalism,
3619-481: The developing world. The genotype 2 strains from Africa can be divided into four clades that correlate with their country of origin: (1) Cameroon and Central African Republic (2) Benin, Ghana and Burkina Faso (3) Gambia, Guinea, Guinea-Bissau and Senegal (4) Madagascar. There is also strong evidence for the dissemination of HCV genotype 2 from West Africa to the Caribbean by the trans-Atlantic slave trade . Genotype 3
3696-422: The electronic density of states. The two theories represent two ways to build up the electron configuration of the molecule. For valence bond theory, the atomic hybrid orbitals are filled with electrons first to produce a fully bonded valence configuration, followed by performing a linear combination of contributing structures ( resonance ) if there are several of them. In contrast, for molecular orbital theory
3773-514: The envelope of HCV and are stabilized by disulfide bonds . E2 is globular and seems to protrude 6 nm out from the envelope membrane according to electron microscope images. These glycoproteins play an important role in the interactions hepatitis C has with the immune system. A hypervariable region , the hypervariable region 1 (HVR1) can be found on the E2 glycoprotein. HVR1 is flexible and quite accessible to surrounding molecules. HVR1 helps E2 shield
3850-412: The feasibility and speed of computer calculations compared to nonorthogonal valence bond orbitals. Evaluation of bond covalency is dependent on the basis set for approximate quantum-chemical methods such as COOP (crystal orbital overlap population), COHP (Crystal orbital Hamilton population), and BCOOP (Balanced crystal orbital overlap population). To overcome this issue, an alternative formulation of
3927-417: The genus Hepacivirus , a member of the family Flaviviridae . Before 2011, it was considered to be the only member of this genus. However a member of this genus has been discovered in dogs : canine hepacivirus . There is also at least one virus in this genus that infects horses. Several additional viruses in the genus have been described in bats and rodents. The hepatitis C virus particle consists of
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#17328955379844004-400: The greater the value of C A , B , {\displaystyle C_{\mathrm {A,B} },} the higher the overlap of the selected atomic bands, and thus the electron density described by those orbitals gives a more covalent A−B bond. The quantity C A , B {\displaystyle C_{\mathrm {A,B} }}
4081-447: The hepatitis C virus include Core protein, E1 and E2; nonstructural proteins include NS2 , NS3 , NS4A , NS4B , NS5A , and NS5B . The proteins of this virus are arranged along the genome in the following order: N terminal-core-envelope (E1)–E2–p7-nonstructural protein 2 (NS2)–NS3–NS4A–NS4B–NS5A–NS5B–C terminal. The mature nonstructural proteins (NS2 to NS5B) generation relies on the activity of viral proteinases. The NS2/NS3 junction
4158-413: The mass center of | n A , l A ⟩ {\displaystyle |n_{\mathrm {A} },l_{\mathrm {A} }\rangle } levels of atom A with respect to the mass center of | n B , l B ⟩ {\displaystyle |n_{\mathrm {B} },l_{\mathrm {B} }\rangle } levels of atom B is given as where
4235-645: The narrow host range of HCV. The use of replicons has been successful but these have only been recently discovered. HCV, as with most RNA viruses, exists as a viral quasispecies , making it very difficult to isolate a single strain or receptor type for study. Current research is focused on small-molecule inhibitors of the viral protease , RNA polymerase and other nonstructural genes. Two agents— boceprevir by Merck and telaprevir by Vertex Pharmaceuticals —both inhibitors of NS3 protease were approved for use on May 13, 2011, and May 23, 2011, respectively. A possible association between low Vitamin D levels and
4312-417: The nucleotide sites over the complete genome. The difference in genomic composition of subtypes of a genotype is usually 20–25%. Subtypes 1a and 1b are found worldwide and cause 60% of all cases. 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
4389-458: The number of π electrons fit the formula 4 n + 2 (where n is an integer), it attains extra stability and symmetry. In benzene , the prototypical aromatic compound, there are 6 π bonding electrons ( n = 1, 4 n + 2 = 6). These occupy three delocalized π molecular orbitals ( molecular orbital theory ) or form conjugate π bonds in two resonance structures that linearly combine ( valence bond theory ), creating
4466-512: The other genotypes (2, 3, 5 and 6). The duration of standard interferon-based therapy for genotypes 1 and 4 is 48 weeks, whereas treatment for genotypes 2 and 3 is completed in 24 weeks. Sustained virological responses occur in 70% of genotype 1 cases, ~90% of genotypes 2 and 3, ~65% of genotype 4 and ~80% of genotype 6. In addition, people of African descent are much less likely to respond to treatment when infected with genotypes 1 or 4. The substantial proportion of this lack of response to treatment
4543-427: The quantum theory of the atom; the outer shell of a carbon atom is the n = 2 shell, which can hold eight electrons, whereas the outer (and only) shell of a hydrogen atom is the n = 1 shell, which can hold only two. While the idea of shared electron pairs provides an effective qualitative picture of covalent bonding, quantum mechanics is needed to understand the nature of these bonds and predict
4620-463: The reduction in the rate of spread once screening for HCV in blood products was implemented in the 1990s, it would seem that previously blood transfusion was an important method of spread. Additional work is required to determine the dates of evolution of the various genotypes and the timing of their spread across the globe. Unlike hepatitis A and B, there is currently no vaccine to prevent hepatitis C infection. The study of HCV has been hampered by
4697-544: The same cell, genetic recombination may occur. Although infrequent, HCV recombination has been observed between different genotypes, between subtypes of the same genotype and even between strains of the same subtype. Hepatitis C virus is predominantly a blood-borne virus , with very low risk of sexual or vertical transmission . Because of this mode of spread the key groups at risk are intravenous drug users (IDUs), recipients of blood products and sometimes patients on haemodialysis . Common setting for transmission of HCV
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#17328955379844774-708: The sharing of electron pairs between atoms (and in 1926 he also coined the term " photon " for the smallest unit of radiant energy). He introduced the Lewis notation or electron dot notation or Lewis dot structure , in which valence electrons (those in the outer shell) are represented as dots around the atomic symbols. Pairs of electrons located between atoms represent covalent bonds. Multiple pairs represent multiple bonds, such as double bonds and triple bonds . An alternative form of representation, not shown here, has bond-forming electron pairs represented as solid lines. Lewis proposed that an atom forms enough covalent bonds to form
4851-661: The sharing of electrons over more than two atoms is said to be delocalized . The term covalence in regard to bonding was first used in 1919 by Irving Langmuir in a Journal of the American Chemical Society article entitled "The Arrangement of Electrons in Atoms and Molecules". Langmuir wrote that "we shall denote by the term covalence the number of pairs of electrons that a given atom shares with its neighbors." The idea of covalent bonding can be traced several years before 1919 to Gilbert N. Lewis , who in 1916 described
4928-530: The simple molecular orbital approach neglects electron correlation while the simple valence bond approach overestimates it. Modern calculations in quantum chemistry usually start from (but ultimately go far beyond) a molecular orbital rather than a valence bond approach, not because of any intrinsic superiority in the former but rather because the MO approach is more readily adapted to numerical computations. Molecular orbitals are orthogonal, which significantly increases
5005-406: The strongest covalent bonds and are due to head-on overlapping of orbitals on two different atoms. A single bond is usually a σ bond. Pi (π) bonds are weaker and are due to lateral overlap between p (or d) orbitals. A double bond between two given atoms consists of one σ and one π bond, and a triple bond is one σ and two π bonds. Covalent bonds are also affected by the electronegativity of
5082-531: The structures and properties of simple molecules. Walter Heitler and Fritz London are credited with the first successful quantum mechanical explanation of a chemical bond ( molecular hydrogen ) in 1927. Their work was based on the valence bond model, which assumes that a chemical bond is formed when there is good overlap between the atomic orbitals of participating atoms. Atomic orbitals (except for s orbitals) have specific directional properties leading to different types of covalent bonds. Sigma (σ) bonds are
5159-715: The third electron is in an anti-bonding orbital which cancels out half of the bond formed by the other two electrons. Another example of a molecule containing a 3-electron bond, in addition to two 2-electron bonds, is nitric oxide , NO. The oxygen molecule, O 2 can also be regarded as having two 3-electron bonds and one 2-electron bond, which accounts for its paramagnetism and its formal bond order of 2. Chlorine dioxide and its heavier analogues bromine dioxide and iodine dioxide also contain three-electron bonds. Molecules with odd-electron bonds are usually highly reactive. These types of bond are only stable between atoms with similar electronegativities. There are situations whereby
5236-621: The tropics, where people receive large number of insect bites. Identification of the origin of this virus has been difficult but genotypes 1 and 4 appear to share a common origin. A Bayesian analysis suggests that the major genotypes diverged about 300–400 years ago from the common ancestor virus. The minor genotypes diverged about 200 years ago from their major genotypes. All of the extant genotypes appear to have evolved from genotype 1 subtype 1b. A study of genotype 6 strains suggests an earlier date of evolution: approximately 1,100 to 1,350 years Before Present . The estimated rate of mutation
5313-552: The understanding of reaction mechanisms . As molecular orbital theory builds the molecular wavefunction out of delocalized orbitals, it is more suited for the calculation of ionization energies and the understanding of spectral absorption bands . At the qualitative level, both theories contain incorrect predictions. Simple (Heitler–London) valence bond theory correctly predicts the dissociation of homonuclear diatomic molecules into separate atoms, while simple (Hartree–Fock) molecular orbital theory incorrectly predicts dissociation into
5390-528: The viral protein NS4B. The core protein associates with lipid droplets and utilises microtubules and dyneins to alter their location to a perinuclear distribution. Release from the hepatocyte may involve the VLDL secretory pathway. Another hypothesis states that the viral particle may be secreted from the endoplasmic reticulum through the endosomal sorting complex required for transport (ESCRT) pathway. This pathway
5467-431: The virus from the immune system. It prevents CD81 from latching onto its respective receptor on the virus. In addition, E2 can shield E1 from the immune system. Although HVR1 is quite variable in amino acid sequence, this region has similar chemical, physical, and conformational characteristics across many E2 glycoproteins. Hepatitis C virus has a positive sense single-stranded RNA genome . The genome consists of
5544-421: The virus is thought to be able to associate with apolipoproteins . It could surround itself with lipoproteins, partially covering up E1 and E2. Recent research indicates that these apolipoproteins interact with scavenger receptor B1 (SR-B1). SR-B1 is able to remove lipids from the lipoproteins around the virus to better allow for HVR1 contact. Claudin 1, which is a tight-junction protein , and CD81 link to create
5621-445: The virus it is considered a quasispecies rather than a conventional virus species. Entry into host cells occur through complex interactions between virions, especially through their glycoproteins, and cell-surface molecules CD81 , LDL receptor , SR-BI , DC-SIGN , Claudin-1 , and Occludin . The envelope of HCV is similar to very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). Because of this similarity,
5698-438: Was 1.8 × 10 . An experimental study estimated the mutation rate at 2.5–2.9 × 10 base substitutions per site per year. This genotype may be the ancestor of the other genotypes. A study of European, US and Japanese isolates suggested that the date of origin of genotype 1b was approximately in the year 1925. The estimated dates of origin of types 2a and 3a were 1917 and 1943 respectively. The time of divergence of types 1a and 1b
5775-543: Was announced that Harvey J. Alter , Michael Houghton , and Charles M. Rice had been awarded the 2020 Nobel Prize in Physiology or Medicine for the discovery of HCV. Covalently bonded A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms . These electron pairs are known as shared pairs or bonding pairs . The stable balance of attractive and repulsive forces between atoms, when they share electrons ,
5852-544: Was approved by the FDA on December 6, 2013. It has been reported to be the first drug that has demonstrated safety and efficacy to treat certain types of HCV infection without the need for co-administration of interferon. On November 22, the FDA approved simeprevir for use in combination with peginterferon-alfa and ribavirin . Simeprevir has been approved in Japan for the treatment of chronic hepatitis C infection, genotype 1. There
5929-404: Was estimated to be 200–300 years. A study of genotype 1a and 1b estimated the dates of origin to be 1914–1930 for type 1a and 1911–1944 for type 1b. Both types 1a and 1b underwent massive expansions in their effective population size between 1940 and 1960. The expansion of HCV subtype 1b preceded that of subtype 1a by at least 16 years. Both types appear to have spread from the developed world to
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