Urumin

Last updated
Urumin
Names
Other names
IPLRGAFINGRWDSQCHRFSNGAIACA; H-Ile-Pro-Leu-Arg-Gly-Ala-Phe-Ile-Asn-Gly-Arg-Trp-Asp-Ser-Gln-Cys-His-Arg-Phe-Ser-Asn-Gly-Ala-Ile-Ala-Cys-Ala-OH
Identifiers
3D model (JSmol)
  • InChI=1S/C129H198N42O35S2/c1-13-63(6)100(133)125(204)171-43-27-37-92(171)122(201)163-80(44-62(4)5)112(191)154-76(34-24-40-141-127(134)135)106(185)145-54-96(177)149-66(9)103(182)157-82(46-71-30-20-17-21-31-71)117(196)170-102(65(8)15-3)124(203)164-86(50-95(132)176)108(187)147-56-98(179)153-77(35-25-41-142-128(136)137)109(188)159-83(47-72-52-144-75-33-23-22-32-74(72)75)114(193)162-87(51-99(180)181)116(195)166-88(57-172)118(197)156-79(38-39-93(130)174)111(190)168-91(60-208)121(200)160-84(48-73-53-140-61-148-73)115(194)155-78(36-26-42-143-129(138)139)110(189)158-81(45-70-28-18-16-19-29-70)113(192)165-89(58-173)119(198)161-85(49-94(131)175)107(186)146-55-97(178)150-67(10)105(184)169-101(64(7)14-2)123(202)151-68(11)104(183)167-90(59-207)120(199)152-69(12)126(205)206/h16-23,28-33,52-53,61-69,76-92,100-102,144,172-173,207-208H,13-15,24-27,34-51,54-60,133H2,1-12H3,(H2,130,174)(H2,131,175)(H2,132,176)(H,140,148)(H,145,185)(H,146,186)(H,147,187)(H,149,177)(H,150,178)(H,151,202)(H,152,199)(H,153,179)(H,154,191)(H,155,194)(H,156,197)(H,157,182)(H,158,189)(H,159,188)(H,160,200)(H,161,198)(H,162,193)(H,163,201)(H,164,203)(H,165,192)(H,166,195)(H,167,183)(H,168,190)(H,169,184)(H,170,196)(H,180,181)(H,205,206)(H4,134,135,141)(H4,136,137,142)(H4,138,139,143)/t63-,64-,65-,66-,67-,68-,69-,76-,77-,78-,79-,80-,81-,82-,83-,84-,85-,86-,87-,88-,89-,90-,91-,92-,100-,101-,102-/m0/s1
    Key: QLPKBNCTTOVOBP-QZGABZBFSA-N
  • N[C@@]([H])([C@]([H])(CC)C)C(=O)N1[C@@]([H])(CCC1)C(=O)N[C@@]([H])(CC(C)C)C(=O)N[C@@]([H])(CCCNC(=N)N)C(=O)NCC(=O)N[C@@]([H])(C)C(=O)N[C@@]([H])(Cc1ccccc1)C(=O)N[C@@]([H])([C@]([H])(CC)C)C(=O)N[C@@]([H])(CC(=O)N)C(=O)NCC(=O)N[C@@]([H])(CCCNC(=N)N)C(=O)N[C@@]([H])(CC(=CN2)C1=C2C=CC=C1)C(=O)N[C@@]([H])(CC(=O)O)C(=O)N[C@@]([H])(CO)C(=O)N[C@@]([H])(CCC(=O)N)C(=O)N[C@@]([H])(CS)C(=O)N[C@@]([H])(CC1=CN=C-N1)C(=O)N[C@@]([H])(CCCNC(=N)N)C(=O)N[C@@]([H])(Cc1ccccc1)C(=O)N[C@@]([H])(CO)C(=O)N[C@@]([H])(CC(=O)N)C(=O)NCC(=O)N[C@@]([H])(C)C(=O)N[C@@]([H])([C@]([H])(CC)C)C(=O)N[C@@]([H])(C)C(=O)N[C@@]([H])(CS)C(=O)N[C@@]([H])(C)C(=O)O
Properties
C129H198N42O35S2
Molar mass 2961.38 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Urumin is a naturally occurring 27-amino acid virucidal host defense peptide against the human influenza A virus. [1] It was discovered and isolated from the skin of Hydrophylax bahuvistara , a species of frog found in South India, by a team of Emory University researchers. [1] The team that discovered urumin tested the peptide against 8 different H1N1 and 4 different H3N2 viruses, as well as various other influenza viruses. [1] The peptide specifically targets the evolutionarily conserved H1 hemagglutinin stalk region of H1-containing influenza A viruses. [1] Additionally, urumin was active against drug-resistant influenza A viruses, that were resistant against oseltamivir, zanamivir and peramivir . [1] While its mechanism of action is not fully understood, urumin seems to inhibit viral growth by physically destroying influenza A virions, and is able to protect naive mice from doses of influenza A infection as high as 2 times the LD50. [1] Because of its specific targeting of the hemagglutinin stalk region of the influenza A virus, the mechanism of action of urumin is similar to that of antibodies induced in the body by universal influenza vaccines. [1] Urumin was also tested for toxicity against erythrocytes and showed a TD50 of 2,450 μM and TI of 664.7, indicating a favorable toxicity profile against erythrocytes. [1] As such, urumin may represent the basis for a potential first-line antiviral treatment against influenza A, particularly in the context of influenza outbreaks, [1] although the discoverers of the peptide have stated that urumin is far from becoming an anti-flu drug. [2] Urumin was named after Urumi, a sword used in Kalaripayattu, the martial art of Kerala, where it was discovered. [3]

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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. Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotic, 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.

<i>Influenza A virus</i> Species of virus

Influenza A virus (IAV) causes influenza in birds and some mammals, and is the only species of the genus Alphainfluenzavirus of the virus family Orthomyxoviridae. Strains of all subtypes of influenza A virus have been isolated from wild birds, although disease is uncommon. Some isolates of influenza A virus cause severe disease both in domestic poultry and, rarely, in humans. Occasionally, viruses are transmitted from wild aquatic birds to domestic poultry, and this may cause an outbreak or give rise to human influenza pandemics.

<span class="mw-page-title-main">Hemagglutinin (influenza)</span> Hemagglutinin of influenza virus

Influenza hemagglutinin (HA) or haemagglutinin[p] is a homotrimeric glycoprotein found on the surface of influenza viruses and is integral to its infectivity.

<i>Orthomyxoviridae</i> Family of RNA viruses including the influenza viruses

Orthomyxoviridae is a family of negative-sense RNA viruses. It includes seven genera: Alphainfluenzavirus, Betainfluenzavirus, Gammainfluenzavirus, Deltainfluenzavirus, Isavirus, Thogotovirus, and Quaranjavirus. The first four genera contain viruses that cause influenza in birds and mammals, including humans. Isaviruses infect salmon; the thogotoviruses are arboviruses, infecting vertebrates and invertebrates. The Quaranjaviruses are also arboviruses, infecting vertebrates (birds) and invertebrates (arthropods).

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<span class="mw-page-title-main">Influenza A virus subtype H1N1</span> Subtype of Influenza A virus

In virology, influenza A virus subtype H1N1 (A/H1N1) is a subtype of influenza A virus. Major outbreaks of H1N1 strains in humans include the Spanish flu, the 1977 Russian flu pandemic and the 2009 swine flu pandemic. It is an orthomyxovirus that contains the glycoproteins hemagglutinin and neuraminidase. For this reason, they are described as H1N1, H1N2 etc., depending on the type of H or N antigens they express with metabolic synergy. Hemagglutinin causes red blood cells to clump together and binds the virus to the infected cell. Neuraminidase is a type of glycoside hydrolase enzyme which helps to move the virus particles through the infected cell and assist in budding from the host cells.

<span class="mw-page-title-main">Urumi</span> Sword

Urumi is a sword with a flexible, whip-like blade, originating in modern-day Kerala in the Indian subcontinent. It is thought to have existed from as early as the Sangam period.

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<span class="mw-page-title-main">H5N1 genetic structure</span>

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Antigenic variation or antigenic alteration refers to the mechanism by which an infectious agent such as a protozoan, bacterium or virus alters the proteins or carbohydrates on its surface and thus avoids a host immune response, making it one of the mechanisms of antigenic escape. It is related to phase variation. Antigenic variation not only enables the pathogen to avoid the immune response in its current host, but also allows re-infection of previously infected hosts. Immunity to re-infection is based on recognition of the antigens carried by the pathogen, which are "remembered" by the acquired immune response. If the pathogen's dominant antigen can be altered, the pathogen can then evade the host's acquired immune system. Antigenic variation can occur by altering a variety of surface molecules including proteins and carbohydrates. Antigenic variation can result from gene conversion, site-specific DNA inversions, hypermutation, or recombination of sequence cassettes. The result is that even a clonal population of pathogens expresses a heterogeneous phenotype. Many of the proteins known to show antigenic or phase variation are related to virulence.

<i>Indirana semipalmata</i> Species of amphibian

Indirana semipalmata is a species of frog endemic to the Western Ghats region of southern India. They are small frogs, reaching lengths of about 36 mm (1.4 in) from snout to vent. The species breeds during the monsoons, laying their eggs on moist rocks and tree bark. Their tadpoles are terrestrial - hatching, feeding, and undergoing metamorphosis without ever entering any standing bodies of water.

<span class="mw-page-title-main">Nitazoxanide</span> Chemical compound

Nitazoxanide, sold under the brand name Alinia among others, is a broad-spectrum antiparasitic and broad-spectrum antiviral medication that is used in medicine for the treatment of various helminthic, protozoal, and viral infections. It is indicated for the treatment of infection by Cryptosporidium parvum and Giardia lamblia in immunocompetent individuals and has been repurposed for the treatment of influenza. Nitazoxanide has also been shown to have in vitro antiparasitic activity and clinical treatment efficacy for infections caused by other protozoa and helminths; evidence as of 2014 suggested that it possesses efficacy in treating a number of viral infections as well.

<span class="mw-page-title-main">Influenza</span> Infectious disease, often just "the flu"

Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms begin from one to four days after exposure to the virus and last for about 2–8 days. Diarrhea and vomiting can occur, particularly in children. Influenza may progress to pneumonia, which can be caused by the virus or by a subsequent bacterial infection. Other complications of infection include acute respiratory distress syndrome, meningitis, encephalitis, and worsening of pre-existing health problems such as asthma and cardiovascular disease.

<span class="mw-page-title-main">Viral neuraminidase</span>

Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell. Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins. Neuraminidase inhibitors are antiviral agents that inhibit influenza viral neuraminidase activity and are of major importance in the control of influenza.

FI6 is an antibody that targets a protein found on the surface of all influenza A viruses called hemagglutinin. FI6 is the only known antibody found to bind all 16 subtypes of the influenza A virus hemagglutinin and is hoped to be useful for a universal influenza virus therapy.

<span class="mw-page-title-main">H5N1 vaccine</span> Vaccine designed to provide immunity against H5N1 influenza

A H5N1 vaccine is an influenza vaccine intended to provide immunization to influenza A virus subtype H5N1.

Neuraminidase inhibitors inhibit enzymatic activity of the enzyme neuraminidase (sialidase). These type of inhibitors have been introduced as anti-influenza drugs as they prevent the virus from exiting infected cells and thus stop further spreading of the virus. Neuraminidase inhibitors for human neuraminidase (hNEU) have the potential to be useful drugs as the enzyme plays a role in several signaling pathways in cells and is implicated in diseases such as diabetes and cancer.

<span class="mw-page-title-main">Universal flu vaccine</span> Vaccine that prevents infection from all strains of the flu

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<i>Hydrophylax bahuvistara</i> Species of amphibian

Hydrophylax bahuvistara, commonly known as the widespread fungoid frog, is a colourful frog found widespread in peninsular India, distributed in Maharashtra, Karnataka, Goa and Madhya Pradesh. It is very similar to another species with which it overlaps partly in range, Hydrophylax malabaricus.

Esculentin-2CHa is an antimicrobial peptide located outside the epithelial cell's membrane of the skin of many species of amphibians, such as Rana chiricahuensis. This peptide has recently become more important due to its defense response function and its possible application in the treatment of various human pathologies, that range from type 2 diabetes to bacterial and fungi infections. Esculentin-2CHa is a peptide that belongs to the Esculentin-2 family, which is known for its broad-spectrum of antimicrobial activity and its low cytotoxicity to human erythrocytes. However, not much is known about its structures and their relation to the functions these peptides carry out.

References

  1. 1 2 3 4 5 6 7 8 9 Holthausen DJ, Lee SH, Kumar VT, Bouvier NM, Krammer F, Ellebedy AH, Wrammert J, Lowen AC, George S, Pillai MR, Jacob J (2017). "An Amphibian Host Defense Peptide Is Virucidal for Human H1 Hemagglutinin-Bearing Influenza Viruses". Immunity. 46 (4): 587–595. doi: 10.1016/j.immuni.2017.03.018 . PMID   28423338.
  2. SciNews (2017). "Frog Skin Peptide 'Urumin' Kills H1 Influenza Viruses".
  3. Healy, Melissa (18 April 2017). "Why the next flu medicine could come from frog mucus". Los Angeles Times . Retrieved 7 January 2021.