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AHFS/Drugs.com | International Drug Names |
Routes of administration | IV |
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Formula | C19H17N5O2 |
Molar mass | 347.378 g·mol−1 |
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Nafamostatmesylate (INN), a synthetic serine protease inhibitor, it is a short-acting anticoagulant, [1] and is also used for the treatment of pancreatitis. It also has some potential antiviral and anti-cancer properties. [2] Nafamostat is a fast-acting proteolytic inhibitor and used during hemodialysis to prevent the proteolysis of fibrinogen into fibrin. [3] The mechanism of action of Nafamostat is as a slow tight-binding substrate, trapping the target protein in the acyl-enzyme intermediate form, resulting in apparent observed inhibition. [4] [5]
It inhibits a large number of Lys/Arg specific serine proteinases, and is also a tryptase inhibitor, which is implicated in leaking blood vessels which is symptomatic of dengue hemorrhagic fever and of end-stage dengue shock syndrome. [6] It is available in a generic form already used for the treatment of certain bleeding complications in some countries, there are risks of severe complications such as: agranulocytosis, hyperkalemia, and anaphylaxis which must be weighed in non-emergency care. [7] In some countries, it used as a treatment for pancreatitis and pancreatic cancer.[ citation needed ]
This drug has been identified as a potential therapy for COVID-19, [8] with clinical trials in Japan possibly set to begin in March 2020. [9] With evidence that Nafamostat is a potent anti-viral inhibitor in lung cells, a second round of clinical trials in Korea has begun with 10 hospitals participating. [10]
Multiple Phase 2/3 [11] [12] [13] and Phase 3 [14] [15] clinical trials for COVID-19 in different countries are ongoing.
Nelfinavir, sold under the brand name Viracept, is an antiretroviral medication used in the treatment of HIV/AIDS. Nelfinavir belongs to the class of drugs known as protease inhibitors (PIs) and like other PIs is almost always used in combination with other antiretroviral drugs.
Ulinastatin, as an urinary trypsin inhibitor (UTI), is a glycoprotein that is isolated from healthy human urine or synthetically produced and has molecular weight of 25 - 40kDa. Highly purified ulinastatin has been clinically used for the treatment of acute pancreatitis, chronic pancreatitis, Stevens–Johnson syndrome, burns, septic shock, and toxic epidermal necrolysis (TEN).
Transmembrane protease, serine 2 is an enzyme that in humans is encoded by the TMPRSS2 gene. It belongs to the TMPRSS family of proteins, whose members are transmembrane proteins which have a serine protease activity. The TMPRSS2 protein is found in high concentration in the cell membranes of epithelial cells of the lung and of the prostate, but also in the heart, liver and gastrointestinal tract.
Eribulin, sold under the brand name Halaven, is an anticancer medication used to treat breast cancer and liposarcoma.
Camostat is a serine protease inhibitor. Serine protease enzymes have a variety of functions in the body, and so camostat has a diverse range of uses. Camostat is approved in Japan for the treatment of chronic pancreatitis and postoperative reflux esophagitis. The oral proteolytic enzyme inhibitor has been on the market since 1985 under the trade name Foipan Tablets. The manufacturer is Ono Pharmaceutical. The drug is used in the treatment of some forms of cancer and is also effective against some viral infections, as well as inhibiting fibrosis in liver or kidney disease or pancreatitis.
Baricitinib, sold under the brand name Olumiant among others, is an immunomodulatory medication used for the treatment of rheumatoid arthritis, alopecia areata, and COVID-19. It acts as an inhibitor of janus kinase (JAK), blocking the subtypes JAK1 and JAK2.
The 3C-like protease (3CLpro) or main protease (Mpro), formally known as C30 endopeptidase or 3-chymotrypsin-like protease, is the main protease found in coronaviruses. It cleaves the coronavirus polyprotein at eleven conserved sites. It is a cysteine protease and a member of the PA clan of proteases. It has a cysteine-histidine catalytic dyad at its active site and cleaves a Gln–(Ser/Ala/Gly) peptide bond.
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.
NITD008 is an antiviral drug classified as an adenosine analog. It was developed as a potential treatment for flavivirus infections and shows broad spectrum antiviral activity against many related viruses such as dengue virus, West Nile virus, yellow fever virus, Powassan virus, hepatitis C virus, Kyasanur Forest disease virus, Omsk hemorrhagic fever virus, and Zika virus. However, NITD008 proved too toxic in pre-clinical animal testing to be suitable for human trials, but it continues to be used in research to find improved treatments for emerging viral diseases.
Remdesivir, sold under the brand name Veklury, is a broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences. It is administered via injection into a vein. During the COVID‑19 pandemic, remdesivir was approved or authorized for emergency use to treat COVID‑19 in numerous countries.
Drug repositioning is the repurposing of an approved drug for the treatment of a different disease or medical condition than that for which it was originally developed. This is one line of scientific research which is being pursued to develop safe and effective COVID-19 treatments. Other research directions include the development of a COVID-19 vaccine and convalescent plasma transfusion.
COVID-19 drug development is the research process to develop preventative therapeutic prescription drugs that would alleviate the severity of coronavirus disease 2019 (COVID-19). From early 2020 through 2021, several hundred drug companies, biotechnology firms, university research groups, and health organizations were developing therapeutic candidates for COVID-19 disease in various stages of preclinical or clinical research, with 419 potential COVID-19 drugs in clinical trials, as of April 2021.
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 and is widely used despite no official FDA approval due to Gilead's refusal to license this drug for veterinary use. An isopropylester pro-drug of GS-441524 - Obeldesivir has been developed by Gilead Sciences and is in Phase III clinical trials. A deuterated form has been developed by Vigonvita Life Sciences and is also in Phase III clinical trials.
Sarah L. Pett is a Professor of Infectious Diseases at University College London. Pett is interested in the immunopathology of infections and the development of optimised treatment pathways for infections. During the COVID-19 pandemic, Pett led a clinical trial that investigated the efficacy of remdesivir as a treatment for coronavirus disease.
Although several medications have been approved in different countries as of April 2022, not all countries have these medications. Patients with mild to moderate symptoms who are in the risk groups can take nirmatrelvir/ritonavir or remdesivir, either of which reduces the risk of serious illness or hospitalization. In the US, the Biden Administration COVID-19 action plan includes the Test to Treat initiative, where people can go to a pharmacy, take a COVID test, and immediately receive free Paxlovid if they test positive.
Berzosertib is a drug originally invented by Vertex Pharmaceuticals and licensed to Merck KGaA, Darmstadt, Germany for development. It acts as a potent inhibitor of the enzyme ataxia telangiectasia and Rad3 related (ATR) and with lower potency as an inhibitor of ATM serine/threonine kinase (ATM). These enzymes are both involved in detecting DNA damage as part of cell cycle checkpoints during cell division. By inhibiting their activity, berzosertib interferes with the ability of rapidly dividing cells to detect damage to DNA, and this makes it useful as a potential treatment for some forms of cancer by causing accumulation of DNA damage in the cancer cells and thus reducing their viability. It has progressed furthest in trials for the treatment of ovarian cancer, though also shows activity against numerous other cancer types.
Nirmatrelvir is an antiviral medication developed by Pfizer which acts as an orally active 3C-like protease inhibitor. It is part of a nirmatrelvir/ritonavir combination used to treat COVID-19 and sold under the brand name Paxlovid.
Onyema Eberechukwu Ogbuagu is an American-born infectious diseases physician, educator, researcher, and clinical trial investigator, who was raised and educated in Nigeria. He is an associate professor at Yale School of Medicine in New Haven, CT and is the director of the Yale AIDS Program clinical trials unit. His research contributions have focused on HIV/AIDS prevention and COVID-19 vaccination and treatment clinical trials. He switched his focus at the beginning of the 2019 COVID pandemic and participated as a principal investigator (PI) on the Pfizer-BioNtech COVID-19 vaccine trials and the Remdesivir SIMPLE trial in 2020 and 2021. In pursuit of his global health component of his career, Ogbuagu also supports postgraduate physician medical education programs in low and middle income countries in sub-Saharan Africa in Rwanda (2013–2018) and Liberia as well as HIV treatment programs in Liberia.
Lufotrelvir (PF-07304814) is an antiviral drug developed by Pfizer which acts as a 3CL protease inhibitor. It is a prodrug with the phosphate group being cleaved in vivo to yield the active agent PF-00835231. Lufotrelvir is in human clinical trials for the treatment of COVID-19, and shows good activity against COVID-19 including several variant strains, but unlike the related drug nirmatrelvir it is not orally active and must be administered by intravenous infusion, and so has been the less favoured candidate for clinical development overall.
Ensitrelvir, sold under the brand name Xocova is an antiviral medication used as a treatment for COVID-19. It was developed by Shionogi in partnership with Hokkaido University and acts as an orally active 3C-like protease inhibitor. It is taken by mouth.