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.
AGILE is a platform trial for early-phase evaluation of new treatments for SARS-CoV-2 infection. The trial platform is a collaboration led by the University of Liverpool, working with the Southampton Clinical Trials Unit, the Liverpool School of Tropical Medicine, the MRC Biostatistics Unit at the University of Cambridge and the National Institute for Health and Care Research (NIHR) Clinical Research Facilities. The AGILE platform is funded by the Medical Research Council, and the Wellcome Trust, with additional funding for specific candidate evaluations from the pharmaceutical industry and Unitaid. The Chief Investigator of the trial is Saye Hock Khoo.
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.
The National Institute for Health and Care Research (NIHR) is the British government's major funder of clinical, public health, social care and translational research. With a budget of over £1.2 billion in 2020–21, its mission is to "improve the health and wealth of the nation through research". The NIHR was established in 2006 under the government's Best Research for Best Health strategy, and is funded by the Department of Health and Social Care. As a research funder and research partner of the NHS, public health and social care, the NIHR complements the work of the Medical Research Council. NIHR focuses on translational research, clinical research and applied health and social care research.
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.
Galidesivir is an antiviral drug, an adenosine analog. It was developed by BioCryst Pharmaceuticals with funding from NIAID, originally intended as a treatment for hepatitis C, but subsequently developed as a potential treatment for deadly filovirus infections such as Ebola virus disease and Marburg virus disease, as well as Zika virus. Currently, galidesivir is under phase 1 human trial in Brazil for coronavirus.
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. The first known case was identified in Wuhan, China, in December 2019. Most scientists believe the SARS-CoV-2 virus entered into human populations through natural zoonosis, similar to the SARS-CoV-1 and MERS-CoV outbreaks, and consistent with other pandemics in human history. Social and environmental factors including climate change, natural ecosystem destruction and wildlife trade increased the likelihood of such zoonotic spillover. The disease quickly spread worldwide, resulting in the COVID-19 pandemic.
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.
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.
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.
The Randomised Evaluation of COVID-19 Therapy is a large-enrollment clinical trial of possible treatments for people in the United Kingdom admitted to hospital with severe COVID-19 infection. The trial was later expanded to Indonesia, Nepal and Vietnam. The trial has tested ten interventions on adults: eight repurposed drugs, one newly developed drug and convalescent plasma.
Long COVID or long-haul COVID is a group of health problems persisting or developing after an initial period of COVID-19 infection. Symptoms can last weeks, months or years and are often debilitating. The World Health Organization defines long COVID as starting three months after the initial COVID-19 infection, but other agencies define it as starting at four weeks after the initial infection.
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.
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.
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.
Ziyad Al-Aly is an American physician and clinical epidemiologist who is currently Director of the Clinical Epidemiology Center and Chief of the Research and Development at the Veterans Affairs St. Louis Health Care System. He is also a clinical epidemiologist at Washington University in St. Louis. He has led multiple studies on long covid and its sequelae.
Jun12682 is an experimental antiviral medication being studied as a potential treatment for COVID-19. It is believed to work by inhibiting SARS-CoV-2 papain-like protease (PLpro), a crucial enzyme for viral replication.
Ibuzatrelvir is an experimental antiviral drug being developed by Pfizer for the treatment of COVID-19. It is a second-generation improvement over nirmatrelvir which has a similar chemical structure. One of the disadvantages of nirmatrelvir is that it has low metabolic stability and must be given in combination with ritonavir to limit its metabolic degradation in the body. Ibuzatrelvir incorporates modifications to the chemical structure of nirmatrelvir that give it enhanced oral bioavailability, so it does not require coadministration with ritonavir.
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