Lumicitabine

Last updated
Lumicitabine
Lumicitabine structure.png
Clinical data
Trade names Lumicitabine
Legal status
Legal status
Identifiers
  • [(2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-2-(chloromethyl)-4-fluoro-3-(2-methylpropanoyloxy)oxolan-2-yl]methyl 2-methylpropanoate
CAS Number
PubChem CID
ChemSpider
UNII
ECHA InfoCard 100.245.433 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C18H25ClFN3O6
Molar mass 433.9 g·mol−1
3D model (JSmol)
  • CC(C)C(=O)OC[C@@]1([C@H]([C@H]([C@@H](O1)N2C=CC(=NC2=O)N)F)OC(=O)C(C)C)CCl
  • InChI=1S/C18H25ClFN3O6/c1-9(2)15(24)27-8-18(7-19)13(28-16(25)10(3)4)12(20)14(29-18)23-6-5-11(21)22-17(23)26/h5-6,9-10,12-14H,7-8H2,1-4H3,(H2,21,22,26)/t12-,13+,14-,18-/m1/s1
  • Key:MJVKYGMNSQJLIN-KYZVSKTDSA-N

Lumicitabine (ALS-8176) is an antiviral drug which was developed as a treatment for respiratory syncytial virus (RSV) and human metapneumovirus (hMPV). It acts as an RNA polymerase inhibitor. [1] While it showed promise in early clinical trials, [2] [3] poor results in Phase IIb trials led to it being discontinued from development for treatment of RSV. [4] Research continues to determine whether it may be useful for the treatment of diseases caused by other RNA viruses, and it has been found to show activity against Nipah virus. [5]

See also

Related Research Articles

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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.

<span class="mw-page-title-main">Ribavirin</span> Antiviral medication

Ribavirin, also known as tribavirin, is an antiviral medication used to treat RSV infection, hepatitis C and some viral hemorrhagic fevers. For hepatitis C, it is used in combination with other medications such as simeprevir, sofosbuvir, peginterferon alfa-2b or peginterferon alfa-2a. Among the viral hemorrhagic fevers it is used for Lassa fever, Crimean–Congo hemorrhagic fever, and Hantavirus infection but should not be used for Ebola or Marburg infections. Ribavirin is taken by mouth or inhaled.

<i>Paramyxoviridae</i> Family of viruses

Paramyxoviridae is a family of negative-strand RNA viruses in the order Mononegavirales. Vertebrates serve as natural hosts. Diseases associated with this family include measles, mumps, and respiratory tract infections. The family has four subfamilies, 17 genera, and 78 species, three genera of which are unassigned to a subfamily.

<i>Henipavirus</i> Genus of RNA viruses

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<span class="mw-page-title-main">Respiratory syncytial virus</span> Species of a virus

Respiratory syncytial virus (RSV), also called human respiratory syncytial virus (hRSV) and human orthopneumovirus, is a common, contagious virus that causes infections of the respiratory tract. It is a negative-sense, single-stranded RNA virus. Its name is derived from the large cells known as syncytia that form when infected cells fuse.

<i>Human metapneumovirus</i> Species of virus

Human metapneumovirus (HMPV) is a negative-sense single-stranded RNA virus of the family Pneumoviridae and is closely related to the Avian metapneumovirus (AMPV) subgroup C. It was isolated for the first time in 2001 in the Netherlands by using the RAP-PCR technique for identification of unknown viruses growing in cultured cells. It is the second most common cause after Respiratory syncytial virus (RSV) of lower respiratory infection in young children.

<span class="mw-page-title-main">Human parainfluenza viruses</span> Viruses that cause human parainfluenza

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<i>Pneumoviridae</i> Family of viruses

Pneumoviridae is a family of negative-strand RNA viruses in the order Mononegavirales. Humans, cattle, and rodents serve as natural hosts. Respiratory tract infections are associated with member viruses such as human respiratory syncytial virus. There are five species in the family which are divided between the genera Metapneumovirus and Orthopneumovirus. The family used to be considered as a sub-family of Paramyxoviridae, but has been reclassified as of 2016.

<span class="mw-page-title-main">Nipah virus infection</span> Disease caused by Nipah virus

A Nipah virus infection is a viral infection caused by the Nipah virus. Symptoms from infection vary from none to fever, cough, headache, shortness of breath, and confusion. This may worsen into a coma over a day or two, and 50 to 75% of those infected die. Complications can include inflammation of the brain and seizures following recovery.

<span class="mw-page-title-main">NS5B inhibitor</span> Class of pharmaceutical drugs

Non-structural protein 5B (NS5B) inhibitors are a class of direct-acting antivirals widely used in the treatment of chronic hepatitis C. Depending on site of action and chemical composition, NS5B inhibitors may be categorized into three classes—nucleoside active site inhibitors (NIs), non-nucleoside allosteric inhibitors, and pyrophosphate analogues. Subsequently, all three classes are then subclassified. All inhibit RNA synthesis by NS5B but at different stages/sites resulting in inability of viral RNA replication. Expression of direct-acting NS5B inhibitors does not take place in cells that are not infected by hepatitis C virus, which seems to be beneficial for this class of drugs.

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Bovine respiratory syncytial virus (BRSV) is pneumovirus closely related to human respiratory syncytial virus (RSV) that is a common cause of respiratory disease in cattle, particularly calves. It is a negative-sense, single-stranded RNA virus that replicates in the cytoplasm of the cell. Similarly to other single-stranded RNA viruses, the genome of BRSV has a high mutation rate, which results in great antigenetic variation. Thus, BRSV can be split into four different subgroups based on antigen expression.

References

  1. Wang G, Deval J, Hong J, Dyatkina N, Prhavc M, Taylor J, Fung A, Jin Z, Stevens SK, Serebryany V, Liu J, Zhang Q, Tam Y, Chanda SM, Smith DB, Symons JA, Blatt LM, Beigelman L (February 2015). "Discovery of 4'-chloromethyl-2'-deoxy-3',5'-di-O-isobutyryl-2'-fluorocytidine (ALS-8176), a first-in-class RSV polymerase inhibitor for treatment of human respiratory syncytial virus infection". Journal of Medicinal Chemistry. 58 (4): 1862–78. doi:10.1021/jm5017279. PMID   25667954.
  2. Brendish NJ, Clark TW (December 2017). "Antiviral treatment of severe non-influenza respiratory virus infection". Current Opinion in Infectious Diseases. 30 (6): 573–578. doi:10.1097/QCO.0000000000000410. PMID   29095723. S2CID   2662061.
  3. Patel K, Kirkpatrick CM, Nieforth KA, Chanda S, Zhang Q, McClure M, Fry J, Symons JA, Blatt LM, Beigelman L, DeVincenzo JP, Huntjens DR, Smith PF (February 2019). "Respiratory syncytial virus-A dynamics and the effects of lumicitabine, a nucleoside viral replication inhibitor, in experimentally infected humans". The Journal of Antimicrobial Chemotherapy. 74 (2): 442–452. doi: 10.1093/jac/dky415 . PMID   30376079.
  4. Taylor P (18 October 2018). "Johnson & Johnson takes $630M hit on RSV drug bought with Alios". fiercebiotech.com.
  5. Lo MK, Amblard F, Flint M, Chatterjee P, Kasthuri M, Li C, Russell O, Verma K, Bassit L, Schinazi RF, Nichol ST, Spiropoulou CF (January 2020). "Potent in vitro activity of β-D-4'-chloromethyl-2'-deoxy-2'-fluorocytidine against Nipah virus". Antiviral Research. 175: 104712. doi:10.1016/j.antiviral.2020.104712. PMC   7054849 . PMID   31935422.