ERDRP-0519

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ERDRP-0519
ERDRP-0519.svg
Legal status
Legal status
Identifiers
  • 2-methyl-N-[4-[(2S)-2-(2-morpholin-4-ylethyl)piperidin-1-yl]sulfonylphenyl]-5-(trifluoromethyl)pyrazole-3-carboxamide
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
Formula C23H30F3N5O4S
Molar mass 529.58 g·mol−1
3D model (JSmol)
  • Cn1c(cc(n1)C(F)(F)F)C(=O)Nc2ccc(cc2)S(=O)(=O)N3CCCC[C@H]3CCN4CCOCC4
  • InChI=1S/C23H30F3N5O4S/c1-29-20(16-21(28-29)23(24,25)26)22(32)27-17-5-7-19(8-6-17)36(33,34)31-10-3-2-4-18(31)9-11-30-12-14-35-15-13-30/h5-8,16,18H,2-4,9-15H2,1H3,(H,27,32)/t18-/m0/s1
  • Key:JVZHTUQIMBYDSX-SFHVURJKSA-N

ERDRP-0519 is an antiviral drug which is the first drug specifically developed to target the measles morbillivirus. It acts as an inhibitor of the viral enzyme RNA polymerase which is essential for viral replication, and in animal studies showed good oral bioavailability and protected ferrets from otherwise lethal doses of a morbillivirus when administered up to three days after infection. [1] [2]

Contents

History

The research was done at Georgia State University and the Paul Ehrlich Institute. [3]

See also

Related Research Articles

<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, three of which are unassigned to a subfamily, and 78 species.

Hepatitis D is a type of viral hepatitis caused by the hepatitis delta virus (HDV). HDV is one of five known hepatitis viruses: A, B, C, D, and E. HDV is considered to be a satellite because it can propagate only in the presence of the hepatitis B virus (HBV). Transmission of HDV can occur either via simultaneous infection with HBV (coinfection) or superimposed on chronic hepatitis B or hepatitis B carrier state (superinfection).

<i>Morbillivirus</i> Genus of viruses

Morbillivirus is a genus of viruses in the order Mononegavirales, in the family Paramyxoviridae. Humans, dogs, cats, cattle, seals, and cetaceans serve as natural hosts. This genus includes six species, with a seventh species being extinct. Diseases in humans associated with viruses classified in this genus include measles; in animals, they include acute febrile respiratory tract infection and Canine distemper. In 2013, a wave of increased death among the Common bottlenose dolphin population was attributed to morbillivirus.

<span class="mw-page-title-main">Hepatitis C virus</span> Species of virus

The hepatitis C virus (HCV) is a small, 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 and lymphomas in humans.

<span class="mw-page-title-main">Measles virus</span> Species of virus

The measles virus (MV), with scientific name Morbillivirus hominis, is a single-stranded, negative-sense, enveloped, non-segmented RNA virus of the genus Morbillivirus within the family Paramyxoviridae. It is the cause of measles. Humans are the natural hosts of the virus; no animal reservoirs are known to exist.

<span class="mw-page-title-main">H5N1 genetic structure</span> Genetic structure of Influenza A virus

The genetic structure of H5N1, a highly pathogenic avian influenza virus, is characterized by a segmented RNA genome consisting of eight gene segments that encode for various viral proteins essential for replication, host adaptation, and immune evasion.

<span class="mw-page-title-main">Herpes simplex virus</span> Species of virus

Herpes simplex virus1 and 2, also known by their taxonomic names Human alphaherpesvirus 1 and Human alphaherpesvirus 2, are two members of the human Herpesviridae family, a set of viruses that produce viral infections in the majority of humans. Both HSV-1 and HSV-2 are very common and contagious. They can be spread when an infected person begins shedding the virus.

<span class="mw-page-title-main">RNA-dependent RNA polymerase</span> Enzyme that synthesizes RNA from an RNA template

RNA-dependent RNA polymerase (RdRp) or RNA replicase is an enzyme that catalyzes the replication of RNA from an RNA template. Specifically, it catalyzes synthesis of the RNA strand complementary to a given RNA template. This is in contrast to typical DNA-dependent RNA polymerases, which all organisms use to catalyze the transcription of RNA from a DNA template.

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

Simeprevir, sold under the brand name Olysio among others, is a medication used in combination with other medications for the treatment of hepatitis C. It is specifically used for hepatitis C genotype 1 and 4. Medications it is used with include sofosbuvir or ribavirin and peginterferon-alfa. Cure rates are in 80s to 90s percent. It may be used in those who also have HIV/AIDS. It is taken by mouth once daily for typically 12 weeks.

<span class="mw-page-title-main">Favipiravir</span> Experimental antiviral drug with potential activity against RNA viruses

Favipiravir, sold under the brand name Avigan among others, is an antiviral medication used to treat influenza in Japan. It is also being studied to treat a number of other viral infections, including SARS-CoV-2. Like the experimental antiviral drugs T-1105 and T-1106, it is a pyrazinecarboxamide derivative.

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

Filibuvir was a non-nucleoside orally available NS5B inhibitor developed by Pfizer for the treatment of hepatitis C. It binds to the non-catalytic Thumb II allosteric pocket of NS5B viral polymerase and causes a decrease in viral RNA synthesis. It is a potent and selective inhibitor, with a mean IC50 of 0.019 μM against genotype 1 polymerases. Several filibuvir-resistant mutations have been identified, M423 being the most common that occurred after filibuvir monotherapy. It was intended to be taken twice-daily.

<span class="mw-page-title-main">MK-608</span> Chemical compound

MK-608 is an antiviral drug, an adenosine analog. It was originally developed by Merck & Co. as a treatment for hepatitis C, but despite promising results in animal studies, it was ultimately unsuccessful in clinical trials. Subsequently it has been widely used in antiviral research and has shown activity against a range of viruses, including Dengue fever, tick-borne encephalitis virus, poliovirus, and most recently Zika virus, in both in vitro and animal models. Since it has already failed in human clinical trials previously, it is unlikely MK-608 itself will be developed as an antiviral medication, but the continuing lack of treatment options for these emerging viral diseases means that much research continues using MK-608 and related antiviral drugs.

Feline morbillivirus comes from the genus Morbillivirus, specifically influencing wild and domestic cats. The first report of a Feline morbillivirus outbreak occurred in Hong Kong in 2012. Approximately 10% of stray cats in Hong Kong and mainland China were reported to possess the virus at the time with additional infections found in Japan as well. 40% of cats tested in Japan were Fmo-PV positive and exhibited early symptoms of kidney failure. While the first cases of Feline morbillivirus were found in China, Hong Kong and Japan, the virus can also be found in Italy, Germany, and the United States. Feline morbillivirus exhibits a substantial amount of genetic diversity, yet cases in Japan and Hong Kong proved to have identical nucleotide sequences. It is also hypothesized that the morbillivirus has high adaptability due to its presence in multiple species. It is often found in dogs, cats, cattle, whales, dolphins, porpoises, and even humans. It likely originated from an ancestral version and underwent viral evolution to adapt to transmission in different species. Other common morbilliviruses include measles, rinderpest virus, canine distemper virus and peste des petits ruminants virus.

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

Lobucavir is an antiviral drug that shows broad-spectrum activity against herpesviruses, hepatitis B and other hepadnaviruses, HIV/AIDS and cytomegalovirus. It initially demonstrated positive results in human clinical trials against hepatitis B with minimal adverse effects but was discontinued from further development following the discovery of increased risk of cancer associated with long-term use in mice. Although this carcinogenic risk is present in other antiviral drugs, such as zidovudine and ganciclovir that have been approved for clinical use, development was halted by Bristol-Myers Squibb, its manufacturer.

<span class="mw-page-title-main">GS-6620</span> Chemical compound

GS-6620 is an antiviral drug which is a nucleotide analogue. It was developed for the treatment of Hepatitis C but while it showed potent antiviral effects in early testing, it could not be successfully formulated into an oral dosage form due to low and variable absorption in the intestines which made blood levels unpredictable. It has however continued to be researched as a potential treatment for other viral diseases such as Ebola virus disease.

<span class="mw-page-title-main">IDX-184</span> Chemical compound

IDX-184 is an antiviral drug which was developed as a treatment for hepatitis C, acting as a NS5B RNA polymerase inhibitor. While it showed reasonable effectiveness in early clinical trials it did not progress past Phase IIb. However research using this drug has continued as it shows potentially useful activity against other emerging viral diseases such as Zika virus, and coronaviruses including MERS, and SARS-CoV-2.

<i>Orthornavirae</i> Kingdom of viruses

Orthornavirae is a kingdom of viruses that have genomes made of ribonucleic acid (RNA), including genes which encode an RNA-dependent RNA polymerase (RdRp). The RdRp is used to transcribe the viral RNA genome into messenger RNA (mRNA) and to replicate the genome. Viruses in this kingdom share a number of characteristics which promote rapid evolution, including high rates of genetic mutation, recombination, and reassortment.

<span class="mw-page-title-main">GS-441524</span> Metabolite of remdesivir

GS-441524 is a nucleoside analogue antiviral drug which was developed by Gilead Sciences. It is the main plasma metabolite of the antiviral prodrug remdesivir, and has a half-life of around 24 hours in human patients. Remdesivir and GS-441524 were both found to be effective in vitro against feline coronavirus strains responsible for feline infectious peritonitis (FIP), a lethal systemic disease affecting domestic cats. Remdesivir was never tested in cats, but GS-441524 has been found to be effective treatment for FIP.

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

Bemnifosbuvir is an antiviral drug invented by Atea Pharmaceuticals and licensed to Roche for clinical development, a novel nucleotide analog prodrug originally developed for the treatment of hepatitis C. Bemnifosbuvir is the orally bioavailable hemisulfate salt of AT-511, which is metabolized in several steps to the active nucleotide triphosphate AT-9010, acting as an RNA polymerase inhibitor and thereby interfering with viral replication. Bemnifosbuvir has been researched for the treatment of coronavirus diseases such as that produced by SARS-CoV-2. It showed good results in early clinical trials but had inconsistent results at later stages. Bemnifosbuvir's Phase III study ended early as it failed to meet its primary endpoint of symptom alleviation and did not decrease viral load. However, the drug was well-tolerated and reduced relative hospitalization risk by 71%.

In the management of HIV/AIDS, HIV capsid inhibitors are antiretroviral medicines that target the capsid shell of the virus. This is in contrast to most current antiretroviral drugs used to treat HIV, which do not directly target the viral capsid. These have also been termed "Capsid-targeting Antivirals", "Capsid Effectors", and "Capsid Assembly Modulators (CAMs)". Because of this, drugs that specifically inhibit the HIV capsid are being developed in order to reduce the replication of HIV, and treat infections that have become resistant to current antiretroviral therapies.

References

  1. White LK, Yoon JJ, Lee JK, Sun A, Du Y, Fu H, et al. (July 2007). "Nonnucleoside inhibitor of measles virus RNA-dependent RNA polymerase complex activity". Antimicrobial Agents and Chemotherapy. 51 (7): 2293–2303. doi:10.1128/AAC.00289-07. PMC   1913224 . PMID   17470652.
  2. Krumm SA, Yan D, Hovingh ES, Evers TJ, Enkirch T, Reddy GP, et al. (April 2014). "An Orally Available, Small-Molecule Polymerase Inhibitor Shows Efficacy Against a Lethal Morbillivirus Infection in a Large Animal Model". Science Translational Medicine. 6 (232): 232ra52. doi:10.1126/scitranslmed.3008517. PMC   4080709 . PMID   24739760.
  3. Grush L (2015-03-24). "New oral drug can stop measles infection before symptoms begin". Fox News. Retrieved 2020-11-18.