Nidoviral Papain-like Protease Domain
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Nidoviral Papain-like Protease Domain
The nidoviral papain-like protease (PLPro or PLP) is a papain-like protease protein domain encoded in the genomes of nidoviruses. It is expressed as part of a large polyprotein from the ORF1a gene and has cysteine protease enzyme, enzymatic activity responsible for proteolysis, proteolytic cleavage of some of the N-terminal viral nonstructural proteins within the polyprotein. A second protease also encoded by ORF1a, called the 3C-like protease or main protease, is responsible for the majority of further cleavages. Coronaviruses have one or two papain-like protease protein domain, domains; in SARS-CoV and SARS-CoV-2, one PLPro domain is located in coronavirus nonstructural protein 3 (nsp3). Arteriviruses have two to three PLP domains. In addition to their protease activity, PLP domains function as deubiquitinating enzymes (DUBs) that can cleave the isopeptide bond found in ubiquitin chains. They are also "deISGylating" enzymes that remove the ubiquitin-like domain ISG15, interferon ...
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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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Coronavirus Nonstructural Protein 3
Coronaviruses are a group of related RNA viruses that cause diseases in mammals and birds. In humans and birds, they cause respiratory tract infections that can range from mild to lethal. Mild illnesses in humans include some cases of the common cold (which is also caused by other viruses, predominantly rhinoviruses), while more lethal varieties can cause SARS, MERS and COVID-19, which is causing the ongoing pandemic. In cows and pigs they cause diarrhea, while in mice they cause hepatitis and encephalomyelitis. Coronaviruses constitute the subfamily ''Orthocoronavirinae'', in the family ''Coronaviridae'', order ''Nidovirales'' and realm ''Riboviria''. They are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome size of coronaviruses ranges from approximately 26 to 32 kilobases, one of the largest among RNA viruses. They have characteristic club-shaped spikes that project from their surface, which in electron m ...
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MERS-CoV
''Middle East respiratory syndrome–related coronavirus'' (''MERS-CoV''), or EMC/2012 ( HCoV-EMC/2012), is the virus that causes Middle East respiratory syndrome (MERS). It is a species of coronavirus which infects humans, bats, and camels. The infecting virus is an enveloped, positive-sense, single-stranded RNA virus which enters its host cell by binding to the DPP4 receptor. The species is a member of the genus ''Betacoronavirus'' and subgenus ''Merbecovirus''. Initially called simply novel coronavirus or nCoV, it was first reported in June 2012 after genome sequencing of a virus isolated from sputum samples from a person who fell ill in a 2012 outbreak of a new flu-like respiratory illness. By July 2015, MERS-CoV cases had been reported in over 21 countries, in Europe, North America and Asia as well as the Middle East. MERS-CoV is one of several viruses identified by the World Health Organization (WHO) as a likely cause of a future epidemic. They list it for urgent research ...
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Pathogen
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ. The term ''pathogen'' came into use in the 1880s. Typically, the term ''pathogen'' is used to describe an ''infectious'' microorganism or agent, such as a virus, bacterium, protozoan, prion, viroid, or fungus. Small animals, such as helminths and insects, can also cause or transmit disease. However, these animals are usually referred to as parasites rather than pathogens. The scientific study of microscopic organisms, including microscopic pathogenic organisms, is called microbiology, while parasitology refers to the scientific study of parasites and the organisms that host them. There are several pathways through which pathogens can invade a host. The principal pathways have different episodic time frames, but soil has the longest ...
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Antiviral Drug
Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do not destroy their target pathogen; instead they inhibit its development. Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotic (also termed antibacterial), antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from viricides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural viricides are produced by some plants such as eucalyptus and Australian tea trees. Medical uses Most of the antiviral drugs now available are designed to help deal with HIV, herpes viruses, th ...
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Drug Target
A biological target is anything within a living organism to which some other entity (like an endogenous ligand (biochemistry), ligand or a drug) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets are proteins and nucleic acids. The definition is context-dependent, and can refer to the biological target of a pharmacological activity, pharmacologically active drug Chemical compound, compound, the receptor target of a hormone (like insulin), or some other target of an external stimulus. Biological targets are most commonly proteins such as enzymes, ion channels, and receptor (biochemistry), receptors. Mechanism The external stimulus (''i.e.'', the drug or ligand) physically binds to ("hits") the biological target. The interaction between the substance and the target may be: * noncovalent bonding, noncovalent – A relatively weak interaction between the stimulus and the target where no chemical bond is forme ...
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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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Essential Gene
Essential genes are indispensable genes for organisms to grow and reproduce offspring under certain environment. However, being ''essential'' is highly dependent on the circumstances in which an organism lives. For instance, a gene required to digest starch is only essential if starch is the only source of energy. Recently, systematic attempts have been made to identify those genes that are absolutely required to maintain life, provided that all nutrients are available. Such experiments have led to the conclusion that the absolutely required number of genes for bacteria is on the order of about 250–300. Essential genes of single-celled organisms encode proteins for three basic functions including genetic information processing, cell envelopes and energy production. Those gene functions are used to maintain a central metabolism, DNA replication, replicate DNA, Translation (biology), translate genes into proteins, maintain a basic cellular structure, and mediate transport processes ...
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Innate Immune System
The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the dominant immune system response found in plants, fungi, insects, and primitive multicellular organisms (see Beyond vertebrates).. The major functions of the innate immune system are to: * recruit immune cells to infection sites by producing chemical factors, including chemical mediators called cytokines * activate the complement cascade to identify bacteria, activate cells, and promote clearance of antibody complexes or dead cells * identify and remove foreign substances present in organs, tissues, blood and lymph, by specialized white blood cells * activate the adaptive immune system through antigen presentation * act as a physical and chemical barrier to infectious agents; via physical measures such as skin and chemical measures such a ...
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ISG15
Interferon-stimulated gene 15 (ISG15) is a 17 kDA secreted protein that in humans is encoded by the ''ISG15'' gene. ISG15 is induced by type I interferon (IFN) and serves many functions, acting both as an extracellular cytokine and an intracellular protein modifier. The precise functions are diverse and vary among species but include potentiation of Interferon gamma (IFN-II) production in lymphocytes, ubiquitin-like conjugation to newly-synthesized proteins and negative regulation of the IFN-I response. Structure The ''ISG15'' gene consists of two exons and encodes for a 17 kDa polypeptide. The immature polypeptide is cleaved at its carboxy terminus, generating a mature 15 kDa product that terminates with a LRLRGG motif, as found in ubiquitin. The tertiary structure of ISG15 also resembles ubiquitin, despite only ~30% sequence homology. Specifically, this structure consists of two ubiquitin-like domains connected by a polypeptide ‘hinge.’ Of note, ISG15 shows substantial s ...
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Ubiquitin-like Domain
Ubiquitin-like proteins (UBLs) are a family of small proteins involved in post-translational modification of other proteins in a cell (biology), cell, usually with a regulatory protein, regulatory function. The UBL protein family derives its name from the first member of the class to be discovered, ubiquitin (Ub), best known for its role in regulating protein degradation through covalent modification of other proteins. Following the discovery of ubiquitin, many additional evolutionarily related members of the group were described, involving parallel regulatory processes and similar chemistry. UBLs are involved in a widely varying array of cellular functions including autophagy, protein trafficking, inflammation and immune responses, transcription (biology), transcription, DNA repair, RNA splicing, and cellular differentiation. Discovery Ubiquitin itself was first discovered in the 1970s and originally named "ubiquitous immunopoietic polypeptide". Subsequently, other proteins with ...
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Ubiquitin
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Four genes in the human genome code for ubiquitin: UBB, UBC, UBA52 and RPS27A. The addition of ubiquitin to a substrate protein is called ubiquitylation (or, alternatively, ubiquitination or ubiquitinylation). Ubiquitylation affects proteins in many ways: it can mark them for degradation via the proteasome, alter their cellular location, affect their activity, and promote or prevent protein interactions. Ubiquitylation involves three main steps: activation, conjugation, and ligation, performed by ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s), respectively. The result of this sequential cascade is to bind ubiquitin to lysine residues on the protein substrate via an isopeptide bond, ...
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