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COVID-19 drug repurposing research

From Wikipedia, the free encyclopedia

Drug repositioning (also called drug repurposing) – the investigation of existing drugs for new therapeutic purposes – is one line of scientific research which is followed to develop safe and effective COVID-19 treatments.[1][2] Other research directions include the development of a COVID-19 vaccine.

Several existing antiviral medications, previously developed or used as treatments for Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), HIV/AIDS, and malaria, are being researched as COVID-19 treatments, with some moving into clinical trials.[3]

In a statement to the journal Nature Biotechnology in February 2020, US National Institutes of Health Viral Ecology Unit chief Vincent Munster said, "The general genomic layout and the general replication kinetics and the biology of the MERS, SARS and [SARS-CoV-2] viruses are very similar, so testing drugs which target relatively generic parts of these coronaviruses is a logical step".[1]

Drug repurposing

Drug repositioning (also known as drug repurposing, re-profiling, re-tasking or therapeutic switching) is the repurposing of an approved drug for the treatment of another disease or medical condition.[4]

Studies

Chloroquine

Chloroquine is an anti-malarial medication that is also used against some auto-immune diseases. On 18 March, the WHO announced that chloroquine and the related hydroxychloroquine would be among the four drugs studied as part of the Solidarity clinical trial.[5] New York governor Andrew Cuomo announced that New York State trials of chloroquine and hydroxychloroquine would begin on 24 March.[6] NYU Langone Medical School is conducting a trial on the safety and efficacy of preventative use of hydroxychloroquine.[7]

Preliminary results had found that chloroquine may be effective and safe in treating COVID-19 associated pneumonia.[8][9][10] The Guangdong Provincial Department of Science and Technology and the Guangdong Provincial Health and Health Commission issued a report stating that chloroquine phosphate "improves the success rate of treatment and shortens the length of patient's hospital stay" and recommended it for people diagnosed with mild, moderate and severe cases of novel coronavirus pneumonia.[11] Two studies in France and China found benefits of treatment with hydroxychloroquine and azithromycin for cases where illness was not yet severe, but a small study in France of 11 patients did not find any evidence that the combination was effective in patients with severe COVID-19 infection.[12][13] One small trial from China found chloroquine may be slightly better than lopinavir/ritonavir.[14]

Preliminary clinical trials to evaluate the safety and efficacy of hydroxychloroquine for treating COVID-19 infection are planned in the United States, but the CDC stated that "the use, dosing, or duration of hydroxychloroquine for prophylaxis or treatment of SARS-CoV-2 infection" were not yet established.[8] On March 28, 2020 the FDA authorized the use of hydroxychloroquine sulfate and chloroquine phosphate under an Emergency Use Authorization (EUA).[15] The treatment has not been approved by the FDA. The experimental treatment is authorized only for emergency use for patients who are hospitalized but are not able to receive treatment in a clinical trial.[16][17]

Favipiravir

Chinese clinical trials in Wuhan and Shenzhen claimed to show that favipiravir was "clearly effective".[18] Of 35 patients in Shenzhen tested negative in a median of 4 days, while the length of illness was 11 days in the 45 patients who did not receive it.[19] In a study conducted in Wuhan on 240 patients with pneumonia half were given favipiravir and half received umifenovir. The researchers found that patients recovered from coughs and fevers faster when treated with favipiravir, but that there was no change in how many patients in each group progressed to more advanced stages of illness that required treatment with a ventilator.[20]

On 22 March 2020, Italy approved the drug for experimental use against COVID-19 and began conducting trials in the three regions most affected by the disease.[21] The Italian Pharmaceutical Agency reminded the public that the existing evidence in support of the drug is scant and preliminary.[22]

The drug may be less effective in severe cases of illness where the virus has already multiplied. It may not be safe for use by pregnant women or those trying to conceive. According to the South China Morning Post, Shinzo Abe has made overtures to the Trump administration about the drug.[19][23]

On 2 April 2020, Germany announced that it will purchase large stockpiles of the drug from Japan, then use the German military to deliver the drug to German university hospitals, where the drug will be used to treat German COVID-19 patients.[24]

Interferon beta

UK biotech firm Synairgen started conducting trials on IFN-β, a drug that was originally developed to treat COPD.[5]

Lopinavir/ritonavir

One study of lopinavir/ritonavir (Kaletra), a combination of the antivirals lopinavir and ritonavir, concluded that "no benefit was observed".[25][26] The drugs were designed to inhibit HIV from replicating by binding to the protease. A team of researchers at the University of Colorado are trying to modify the drugs to find a compound that will bind with the protease of SARS-CoV-2[27]

There are criticisms within the scientific community about directing resources to repurposing drugs specifically developed for HIV/AIDS, since it is unlikely that a drug developed specifically against HIV will work for a very different virus (it is more likely that general-purpose antivirals will work).[1] The WHO included lopinavir/ritonavir in the international Solidarity trial.[5]

Remdesivir

One issue with antiviral treatment is the development of resistance through mutations that can lead to more severe disease and transmission. Some early pretrial studies suggest that Remdesivir may have a high genetic barrier to resistance.[28] Data from clinical trials is expected in April 2020.[29]

There are several clinical trials underway, including two conducted by Cleveland University Hospitals; one for people with moderate illness and another for those with more severe illness.[30] The Feinstein Institute of the Northwell Health system has partnered with Gilead Sciences on phase III clinical trials for remdesivir.[31]

Intravenous vitamin C

There are three ongoing clinical trials of intravenous vitamin C for people who are hospitalized and severely ill with COVID-19; two placebo controlled (China, Canada) and one with no control (Italy).[32]

Azithromycin

New York State began trials for azithromycin on 24 March.[33]

Ciclesonide

Japan's National Center for Global Health and Medicine (NCGM) is planning a clinical trial for Teijin's Alvesco (ciclesonide), an inhaled corticosteroid for asthma, for the treatment of pre-symptomatic patients infected with the novel coronavirus. [34]

APN01

A form of angiotensin-converting enzyme 2, a Phase II trial is underway with 200 patients to be recruited from severe, hospitalized cases in Denmark, Germany, and Austria to determine the effectiveness of the treatment.[35][36]

Repurposed drugs by type

Antiviral drugs

Since SARS-CoV-2 is a virus, considerable scientific attention has been focused on repurposing approved anti-viral drugs that were developed for prior outbreaks such as MERS, SARS, and West Nile virus.[37]

Anti malarial agents

Broad-spectrum agents

  • Ribavirin: ribavirin was recommended for COVID-19 treatment according to Chinese 7th edition guidelines[40]
  • Umifenovir: umifenovir was recommended for COVID-19 treatment according to Chinese 7th edition guidelines[40]

Interferons

Drugs originally developed for SARS

Antibiotics

Some antibiotics that have been identified as potentially repurposable as COVID-19 treatments:[46][47]

Anti-Parasitics

See also

References

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  3. ^ Li, G.; De Clercq, E. (2020). "Therapeutic options for the 2019 novel coronavirus (2019-nCoV)". Nature Reviews. Drug Discovery. 19 (3): 149–150. doi:10.1038/d41573-020-00016-0. PMID 32127666.
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  28. ^ "Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease". doi:10.1128/mBio.00221-18. Cite journal requires |journal= (help)
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  33. ^ a b "Amid Ongoing COVID-19 Pandemic, Governor Cuomo Accepts Recommendation of Army Corps of Engineers for Four Temporary Hospital Sites in New York". governor.ny.gov. 22 March 2020.
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Further reading

  • McCreary, Erin K; Pogue, Jason M (23 March 2020). "COVID-19 Treatment: A Review of Early and Emerging Options". Open Forum Infectious Diseases. doi:10.1093/ofid/ofaa105. ISSN 2328-8957.

External links


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