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Trade names | Xocova |
Other names | S-217622 |
Routes of administration | By mouth |
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Formula | C22H17ClF3N9O2 |
Molar mass | 531.88 g·mol−1 |
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Ensitrelvir, sold under the brand name Xocova is an antiviral medication used as a treatment for COVID-19. [2] [3] [4] [5] It was developed by Shionogi in partnership with Hokkaido University and acts as an orally active 3C-like protease inhibitor. [6] [7] It is taken by mouth. [8] [9] [10]
The most common adverse events include transient decreases in high-density lipoprotein and increases blood triglycerides. [8]
As of 2022 [update] , ensitrelvir had reached Phase III clinical trials. [11] The Japanese government is reportedly considering allowing Shionogi permission to apply for approval for medical use before the final steps of trials are completed, potentially speeding up the release for sale. This conditional early approval system has previously been used in Japan to accelerate the progression to market of other antiviral drugs targeting COVID-19, including remdesivir and molnupiravir. [12] In a study of 428 patients, viral load was reduced, but symptoms were not significantly reduced. [13]
In February 2022, the company sought emergency approval from regulators in Japan. [3] [13]
Shionogi announced they had reached a preliminary agreement to supply 1 million doses to the Japanese government once the drug is approved. The CEO said they could have capacity to make 10 million doses a year. [14]
Ensitrelvir may be effective in treating smell and taste loss from COVID-19 infection. In a 2023 study, the drug was associated with a 39% reduction in these symptoms. [15]
Ensitrelvir was approved for emergency use in Japan in November 2022, [8] [3] [4] before gaining full approval in March 2024. [1] It was approved in Singapore in November 2023. [16]
In April 2023, ensitrelvir was given a "Fast Track" designation from the US Food and Drug Administration. [17]
Ensitrelvir is the International Nonproprietary Name. [18]
Ensitrelvir is being studied for its potential use as post-exposure prophylaxis (PEP) after SARS-CoV-2 exposure. [19] [20] The SCORPIO-PEP trial is a global Phase 3 trial that will evaluate the safety and efficacy of the drug in preventing symptomatic SARS-CoV-2 infection in household contacts of people who tested positive for COVID-19. [20] [21] [22] [23]
An April 2024 pre-clinical study in a mouse model investigating ensitrelvir demonstrated its potential use as a pre-exposure prophylactic (PrEP) against developing COVID-19. When administered 24 hours before viral exposure, a single dose of ensitrelvir significantly increased survival rates, inhibited weight loss, and suppressed viral replication in aged mice. [24]
A retrospective study conducted between November 2022 and July 2023 using a large Japanese health insurance database suggested that ensitrelvir may be effective in reducing hospitalization risk in outpatients at high risk for severe COVID-19. The study found a significantly lower risk of hospitalization and a reduced need for respiratory monitoring and oxygen therapy in the ensitrelvir group compared to the control group. [25]
Protease inhibitors (PIs) are medications that act by interfering with enzymes that cleave proteins. Some of the most well known are antiviral drugs widely used to treat HIV/AIDS, hepatitis C and COVID-19. These protease inhibitors prevent viral replication by selectively binding to viral proteases and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles.
Ritonavir, sold under the brand name Norvir, is an antiretroviral medication used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Ritonavir is a protease inhibitor, though it now mainly serves to boost the potency of other protease inhibitors. It may also be used in combination with other medications to treat hepatitis C and COVID-19. It is taken by mouth.
Post-exposure prophylaxis, also known as post-exposure prevention (PEP), is any preventive medical treatment started after exposure to a pathogen in order to prevent the infection from occurring.
Elvitegravir (EVG) is an integrase inhibitor used to treat HIV infection. It was developed by the pharmaceutical company Gilead Sciences, which licensed EVG from Japan Tobacco in March 2008. The drug gained approval by the U.S. Food and Drug Administration on August 27, 2012, for use in adult patients starting HIV treatment for the first time as part of the fixed dose combination known as Stribild. On September 24, 2014, the FDA approved Elvitegravir as a single pill formulation under the trade name Vitekta. On November 5, 2015, the FDA approved the drug for use in patients affected with HIV-1 as a part of a second fixed dose combination pill known as Genvoya.
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.
Shionogi & Company, Limited is a Japanese pharmaceutical company best known for developing Crestor. Medical supply and brand name also uses katakana (シオノギ).
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.
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.
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.
Baloxavir marboxil, sold under the brand name Xofluza, is an antiviral medication for treatment of influenza A and influenza B. It was approved for medical use both in Japan and in the United States in 2018, and is taken as a single dose by mouth. It may reduce the duration of flu symptoms by about a day, but is prone to selection of resistant mutants that render it ineffectual.
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.
3CLpro-1 is an antiviral drug related to rupintrivir which acts as a 3CL protease inhibitor and was originally developed for the treatment of human enterovirus 71. It is one of the most potent of a large series of compounds developed as inhibitors of the viral enzyme 3CL protease, with an in vitroIC50 of 200 nM. It also shows activity against coronavirus diseases such as SARS and MERS, and is under investigation as a potential treatment agent for the viral disease COVID-19.
Molnupiravir, sold under the brand name Lagevrio, is an antiviral medication that inhibits the replication of certain RNA viruses. It is used to treat COVID‑19 in those infected by SARS-CoV-2. It is taken by mouth.
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.
The treatment and management of COVID-19 combines both supportive care, which includes treatment to relieve symptoms, fluid therapy, oxygen support as needed, and a growing list of approved medications. Highly effective vaccines have reduced mortality related to SARS-CoV-2; however, for those awaiting vaccination, as well as for the estimated millions of immunocompromised persons who are unlikely to respond robustly to vaccination, treatment remains important. Some people may experience persistent symptoms or disability after recovery from the infection, known as long COVID, but there is still limited information on the best management and rehabilitation for this condition.
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.
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.
Nirmatrelvir/ritonavir, sold under the brand name Paxlovid, is a co-packaged medication used as a treatment for COVID‑19. It contains the antiviral medications nirmatrelvir and ritonavir and was developed by Pfizer. Nirmatrelvir inhibits SARS-CoV-2 main protease, while ritonavir is a strong CYP3A inhibitor, slowing down nirmatrelvir metabolism and therefore boosting its effect. It is taken by mouth.
Olgotrelvir (STI-1558) is an experimental antiviral medication being studied as a potential treatment for COVID-19. It is believed to work by inhibiting the SARS-CoV-2 main protease (Mpro), a key enzyme that SARS-CoV-2 needs to replicate, and by blocking viral entry.
SCORPIO-PEP is a 28-day study to assess the prevention of COVID-19 infection in those who have been exposed through household contact.