Coronavirus Spike Protein
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Coronavirus Spike Protein
Spike (S) glycoprotein (sometimes also called spike protein, formerly known as E2) is the largest of the four major structural proteins found in coronaviruses. The spike protein assembles into trimers that form large structures, called spikes or peplomers, that project from the surface of the virion. The distinctive appearance of these spikes when visualized using negative stain transmission electron microscopy, "recalling the solar corona", gives the virus family its name. The function of the spike glycoprotein is to mediate viral entry into the host cell by first interacting with molecules on the exterior cell surface and then fusing the viral and cellular membranes. Spike glycoprotein is a class I fusion protein that contains two regions, known as S1 and S2, responsible for these two functions. The S1 region contains the receptor-binding domain that binds to receptors on the cell surface. Coronaviruses use a very diverse range of receptors; SARS-CoV (which causes SARS) an ...
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Membrane Fusion Protein
Membrane fusion proteins (not to be confused with chimeric or fusion proteins) are proteins that cause fusion of biological membranes. Membrane fusion is critical for many biological processes, especially in eukaryotic development and viral entry. Fusion proteins can originate from genes encoded by infectious enveloped viruses, ancient retroviruses integrated into the host genome, or solely by the host genome. Post-transcriptional modifications made to the fusion proteins by the host, namely addition and modification of glycans and acetyl groups, can drastically affect fusogenicity (the ability to fuse). Fusion in eukaryotes Eukaryotic genomes contain several gene families, of host and viral origin, which encode products involved in driving membrane fusion. While adult somatic cells do not typically undergo membrane fusion under normal conditions, gametes and embryonic cells follow developmental pathways to non-spontaneously drive membrane fusion, such as in placental for ...
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Neutralizing Antibodies
A neutralizing antibody (NAb) is an antibody that defends a cell from a pathogen or infectious particle by neutralizing any effect it has biologically. Neutralization renders the particle no longer infectious or pathogenic. Neutralizing antibodies are part of the humoral response of the adaptive immune system against viruses, intracellular bacteria and microbial toxin. By binding specifically to surface structures (antigen) on an infectious particle, neutralizing antibodies prevent the particle from interacting with its host cells it might infect and destroy. Mechanism In order to enter cells, pathogens, such as circulating viral particles or extracellular bacteria, use molecules on their surfaces to interact with the cell surface receptors of their target cell which allows them to enter the cell and start their replication cycle. Neutralizing antibodies can inhibit infectivity by binding to the pathogen and blocking the molecules needed for cell entry. This can be due to the ...
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Antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope (analogous to a lock) that is specific for one particular epitope (analogous to a key) on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can ''tag'' a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly (for example, by blocking a part of a virus that is essential for its invasion). To allow the immune system to recognize millions of different antigens, the antigen-binding sites at both tips of the antibody come in an equally wide variety. In contrast, the remainder of the antibody is relatively constant. It only occurs in a few vari ...
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Immunogenic
Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted: * Wanted immunogenicity typically relates to vaccines, where the injection of an antigen (the vaccine) provokes an immune response against the pathogen, protecting the organism from future exposure. Immunogenicity is a central aspect of vaccine development. * Unwanted immunogenicity is an immune response by an organism against a therapeutic antigen. This reaction leads to production of anti-drug-antibodies (ADAs), inactivating the therapeutic effects of the treatment and potentially inducing adverse effects. A challenge in biotherapy is predicting the immunogenic potential of novel protein therapeutics. For example, immunogenicity data from high-income countries are not always transferable to low-income and middle-income countries. Another challenge is considering how the immunogenicity of vaccines changes with ...
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Cell Tropism
Endothelial cell tropism or endotheliotropism is a type of tissue tropism or host tropism that characterizes an pathogen's ability to recognize and infect an endothelial cell. Pathogens, such as viruses, can target a specific tissue type or multiple tissue types. Like other cells, the endothelial cell possesses several features that supports a productive viral infection a cell including, cell surface receptors, immune responses, and other virulence factors. Endothelial cells are found in various tissue types such as in the capillaries, veins, and arteries in the human body. As endothelial cells line these blood vessels and critical networks that extend access to various human organ systems, the virus entry into these cells can be detrimental to virus spread across the host system and affect clinical course of disease. Understanding the mechanisms of how viruses attach, enter, and control endothelial functions and host responses inform infectious disease understanding and medical co ...
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Host Range
In biology and medicine, a host is a larger organism that harbours a smaller organism; whether a parasitic, a mutualistic, or a commensalist ''guest'' (symbiont). The guest is typically provided with nourishment and shelter. Examples include animals playing host to parasitic worms (e.g. nematodes), cells harbouring pathogenic (disease-causing) viruses, a bean plant hosting mutualistic (helpful) nitrogen-fixing bacteria. More specifically in botany, a host plant supplies food resources to micropredators, which have an evolutionarily stable relationship with their hosts similar to ectoparasitism. The host range is the collection of hosts that an organism can use as a partner. Symbiosis Symbiosis spans a wide variety of possible relationships between organisms, differing in their permanence and their effects on the two parties. If one of the partners in an association is much larger than the other, it is generally known as the host. In parasitism, the parasite benefits at the ...
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Viral Replication
Viral replication is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. Through the generation of abundant copies of its genome and packaging these copies, the virus continues infecting new hosts. Replication between viruses is greatly varied and depends on the type of genes involved in them. Most DNA viruses assemble in the nucleus while most RNA viruses develop solely in cytoplasm. Viral production / replication Viruses multiply only in living cells. The host cell must provide the energy and synthetic machinery and the low- molecular-weight precursors for the synthesis of viral proteins and nucleic acids. The virus replication occurs in seven stages, namely; # Attachment # Entry, # Uncoating, # Transcription / mRNA production, # Synthesis of virus components, # Virion assembly and # Release (Liberation Stage). Attachment It is the first step of viral replication ...
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Fusion Peptide
Membrane fusion proteins (not to be confused with chimeric or fusion proteins) are proteins that cause fusion of biological membranes. Membrane fusion is critical for many biological processes, especially in eukaryotic development and viral entry. Fusion proteins can originate from genes encoded by infectious enveloped viruses, ancient retroviruses integrated into the host genome, or solely by the host genome. Post-transcriptional modifications made to the fusion proteins by the host, namely addition and modification of glycans and acetyl groups, can drastically affect fusogenicity (the ability to fuse). Fusion in eukaryotes Eukaryotic genomes contain several gene families, of host and viral origin, which encode products involved in driving membrane fusion. While adult somatic cells do not typically undergo membrane fusion under normal conditions, gametes and embryonic cells follow developmental pathways to non-spontaneously drive membrane fusion, such as in placental form ...
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Angiotensin-converting Enzyme 2
Angiotensin-converting enzyme 2 (ACE2) is an enzyme that can be found either attached to the membrane of cells (mACE2) in the intestines, kidney, testis, gallbladder, and heart or in a soluble form (sACE2). Both membrane bound and soluble ACE2 are integral parts of the renin–angiotensin–aldosterone system (RAAS) that exists to keep the body's blood pressure in check. While mACE2 does not appear to factor into the harmful phase of RAAS (the increase of blood pressure), its existence is vital in order for the enzyme ADAM17 to cleave its extracellular domain to create soluble ACE2 (sACE2). Soluble ACE2 lowers blood pressure by catalyzing the hydrolysis of angiotensin II (a vasoconstrictor peptide) into angiotensin (1–7) (a vasodilator) which in turns binds to MasR receptors creating localized vasodilation and hence decreasing blood pressure. This decrease in blood pressure makes the entire process a promising drug target for treating cardiovascular diseases. mACE2 also ser ...
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COVID-19
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was COVID-19 pandemic in Hubei, identified in Wuhan, China, in December 2019. The disease quickly spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 are variable but often include fever, cough, headache, fatigue, breathing difficulties, Anosmia, loss of smell, and Ageusia, loss of taste. Symptoms may begin one to fourteen days incubation period, after exposure to the virus. At least a third of people who are infected Asymptomatic, do not develop noticeable symptoms. Of those who develop symptoms noticeable enough to be classified as patients, most (81%) develop mild to moderate symptoms (up to mild pneumonia), while 14% develop severe symptoms (dyspnea, Hypoxia (medical), hypoxia, or more than 50% lung involvement on imaging), and 5% develop critical symptoms (respiratory failure ...
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SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a provisional name, 2019 novel coronavirus (2019-nCoV), and has also been called the human coronavirus 2019 (HCoV-19 or hCoV-19). First identified in the city of Wuhan, Hubei, China, the World Health Organization declared the outbreak a public health emergency of international concern on January 30, 2020, and a pandemic on March 11, 2020. SARS‑CoV‑2 is a positive-sense single-stranded RNA virus that is contagious in humans. SARS‑CoV‑2 is a virus of the species ''severe acute respiratory syndrome–related coronavirus'' (SARSr-CoV), related to the SARS-CoV-1 virus that caused the 2002–2004 SARS outbreak. Despite its close relation to SARS-CoV-1, its closest known relatives, with which it forms a sister group, are the derived SARS ...
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