COVID-19 drug repurposing research

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This article is about drugs that may be repurposed for treating COVID-19. For potential COVID-19 vaccine, see COVID-19 vaccine. For potential therapeutic drugs for COVID-19, see COVID-19 drug development.

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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 a different disease or medical condition than that for which it was originally developed.[1] This is one line of scientific research which is currently being pursued to develop safe and effective COVID-19 treatments.[2][3] Other research directions include the development of a COVID-19 vaccine[4] and convalescent plasma transfusion.[5]

SARS-CoV-2 has about 66 druggable proteins, each of which has multiple ligand binding sites.[6] Analyzing those binding sites provide the reasonable project of developing effective antiviral drug against COVID‑19 proteins. Of the most important SARS-CoV-2 target proteins are papain-like protease, RNA-dependent RNA polymerase, helicase, S protein, and ADP-ribose diphosphatase.[citation needed] Hussein A A, et al. studied several candidate compounds which then optimized and analyzed for their skeleton similarity with the highest similar approved drugs in order to accelerate a potent anti-SARS-CoV-2 drug development in his preclinical study to be recommended in a clinical study design.[citation needed] Of these potent compounds were the glutathione, lopinavir, and remdesivir.[citation needed]

During the pandemic, 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, were being researched as COVID‑19 treatments, with some moved into clinical trials.[7][8][9]

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[disambiguation needed] 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".[2]

Studies

Chloroquine/Hydroxychloroquine

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.[10] On 19 March, President Donald Trump encouraged the use of chloroquine and hydroxychloroquine during a national press conference. These endorsements led to massive increases in public demand for the drugs [11]. New York Governor Andrew Cuomo announced that New York State trials of chloroquine and hydroxychloroquine would begin on 24 March.[12]

On 28 March, the FDA authorized the use of hydroxychloroquine sulfate and chloroquine phosphate under an Emergency Use Authorization (EUA).[13] The treatment has not been approved by the FDA's clinical trials process and is authorized under the EUA only as an experimental treatment for emergency use in patients who are hospitalized but are not able to receive treatment in a clinical trial.[14][15] The CDC has said that "the use, dosing, or duration of hydroxychloroquine for prophylaxis or treatment of SARS-CoV-2 infection" are not yet established.[16] Doctors have said they are using the drug when "there's no other option".[17] On 9 April, the National Institutes of Health began the first clinical trial to assess whether hydroxychloroquine is safe and effective to treat COVID‑19.[17][18]

On 12 April, a preliminary clinical trial conducted at a hospital in Brazil was stopped when several people given high doses of chloroquine for COVID‑19 infection developed irregular heart rates, causing eleven deaths.[19][20] According to Johns Hopkins' ABX Guide for COVID‑19, "HCQ may cause prolonged QT, and caution should be used in critically ill COVID‑19 patients who may have cardiac dysfunction or if combined with other drugs that cause QT prolongation".[21]

There are several studies underway on prophylactic use of chloroquine, especially in healthcare workers and their families. A Turkish research team in Istanbul is conducting a small study on the use of chloroquine in combination with zinc, vitamin A, vitamin C and vitamin D.[22] Large studies are underway at Duke University and the University of Oxford. NYU Langone Medical School is conducting a trial on the safety and efficacy of preventative use of hydroxychloroquine.[23]

On April 23rd, after one study in New York City concluded, Cuomo said the drug "didn't really have much on an effect on the recovery rate." Hospitals have stopped using the drug as treatment, though it is still being used in research studies.[24] On April 24 the FDA cautioned against using the drug outside a hospital setting or clinical trial after reviewing case reports of adverse effects including ventricular tachycardia, ventricular fibrillation and in some cases death.[25]

Favipiravir

Chinese clinical trials in Wuhan and Shenzhen claimed to show favipiravir was "clearly effective".[26] 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.[27] 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 there was no change in how many patients in each group progressed to more advanced stages of illness (treatment with a ventilator).[28]

On 22 March, Italy approved the drug for experimental use against COVID‑19 and began conducting trials in the three regions most affected by the disease.[29] The Italian Medicines Agency reminded the public that the existing evidence in support of the drug is scant and preliminary.[30] On 2 April, Germany announced that it would purchase the drug from Japan for its stockpile, and use the military to deliver the drug to university hospitals, where the drug will be used to treat COVID‑19 patients.[31] According to the South China Morning Post, Shinzo Abe has made overtures to the Trump administration about purchasing the drug.[32]

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.[27]

Interferon beta

IFN-β will be included in the international Solidarity Trial in combination with the HIV drugs Lopinavir and Ritonavir.[33] as well as the REMAP-CAP [34]

Finnish biotech firm Faron Pharmaceuticals continues to develop INF-beta for ARDS and is currently involved in worldwide initiatives[which?] against COVID-19, including the Solidarity trial.[35]UK biotech firm Synairgen started conducting trials on IFN-β, a drug that was originally developed to treat COPD.[10]

Lopinavir/ritonavir

One study of lopinavir/ritonavir (Kaletra), a combination of the antivirals lopinavir and ritonavir, concluded that "no benefit was observed".[36][37] 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.[38]

There are criticisms within the scientific community about directing resources to repurposing drugs specifically developed for HIV/AIDS.[2] The WHO included lopinavir/ritonavir in the international Solidarity trial.[10]

Remdesivir

Remdesivir was created and developed by Gilead Sciences as a treatment for Ebola virus disease and Marburg virus infections.[39]

During 2020, several clinical trials were underway.[8] The first randomized, placebo-controlled trial of remdesivir in China showed the drug had no clinical or virological benefits compared to the placebo group and caused adverse effects in the remdesivir-treated people, leading to early termination of the trial.[40][41]

On 1 May 2020, the U.S. Food and Drug Administration granted Gilead Emergency Use Authorization of remdesivir to be distributed and used by licensed health care providers to treat adults and children hospitalized with severe COVID‐19.[42] Severe COVID‐19 is defined as patients with an oxygen saturation (SpO2) ≤ 94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO), a heart‐lung bypass machine.[43][42][44] Distribution of remdesivir under the EUA will be controlled by the U.S. government for use consistent with the terms and conditions of the EUA.[42] Gilead will supply remdesivir to authorized distributors, or directly to a U.S. government agency, who will distribute to hospitals and other healthcare facilities as directed by the U.S. Government, in collaboration with state and local government authorities, as needed.[42]

Intravenous vitamin C

According to ClinicalTrials.gov, there are six ongoing clinical trials of intravenous vitamin C for people who are hospitalized and severely ill with COVID‑19; three placebo controlled (China, Canada, US) and three with no control (Italy, US, US).[45]

Azithromycin

New York State began trials for the antibiotic azithromycin on 24 March 2020.[46]

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.[47]

Ciclesonide was found to be promising in tests in Korea.[48]

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.[49][50]

Colchicine

Researchers from the Montreal Heart Institute in Canada are currently studying the role of colchicine in reducing inflammation and pulmonary complications in patients suffering from mild symptoms of COVID‑19.[51] The study, named COLCORONA, is recruiting 6000 adults aged 40 and over who were diagnosed with COVID‑19 and experience mild symptoms not requiring hospitalization.[51][52] Women who are pregnant or breastfeeding or who do not have an effective contraceptive method are not eligible.[52]

Anticoagulants

Several anticoagulants are being tested in Italy. Low-molecular-weight heparin is being widely used to treat patients, prompting the Italian Medicines Agency to publish guidelines on its use.[53] A multicenter study on 300 patients researching the use of enoxaparin sodium at prophylaxis and therapeutic dosages was announced in Italy on April 14.[54]

Famotidine

Famotidine has been suggested as a treatment for COVID-19,[55][56] and a clinical study is currently underway.[57]

Dipyridamole

Dipyridamole is being proposed as a treatment for COVID-19,[55][56] and a clinical trial is currently underway. [58]

Sildenafil

Sildenafil is being proposed as a treatment for COVID-19,[55][56] and a Phase 3 clinical trial is currently underway.[59]

Bezafibrate

Bezafibrate is being proposed as a treatment for COVID-19.[55][56]

Fenofibrate

Fenofibrate is being proposed as a treatment for COVID-19.[55][56]

Cimetidine

Cimetidine has been suggested as a treatment for COVID-19.[55][56]

Niclosamide

Niclosamide was found to be promising in tests in Korea.[48]

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.[60]

Antimalarial agents

Broad-spectrum agents

Interferons

Drugs originally developed for SARS

Antibiotics

Some antibiotics that have been identified as potentially repurposable as COVID‑19 treatments:[67][68]

Antiparasitics

Anti-IL-6

References

  1. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ 2.0 2.1 2.2 Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ 8.0 8.1 Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ 10.0 10.1 10.2 Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  17. ↑ 17.0 17.1 Lua error in package.lua at line 80: module 'strict' not found.
  18. ↑ Clinical trial number NCT04332991 for "Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease (ORCHID)" at ClinicalTrials.gov
  19. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  20. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  21. ↑ see under Treatment section of Coronavirus COVID-19 (SARS-CoV-2); Johns Hopkins ABX Guide (Retrieved April 18, 2020)
  22. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  23. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  24. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  25. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  26. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  27. ↑ 27.0 27.1 Lua error in package.lua at line 80: module 'strict' not found.
  28. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  29. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  30. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  31. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  32. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  33. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  34. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  35. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  36. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  37. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  38. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  39. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  40. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  41. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  42. ↑ 42.0 42.1 42.2 42.3 Lua error in package.lua at line 80: module 'strict' not found.  This article incorporates text from this source, which is in the public domain.
  43. ↑ Lua error in package.lua at line 80: module 'strict' not found.  This article incorporates text from this source, which is in the public domain.
  44. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  45. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  46. ↑ 46.0 46.1 Lua error in package.lua at line 80: module 'strict' not found.
  47. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  48. ↑ 48.0 48.1 Lua error in package.lua at line 80: module 'strict' not found.
  49. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  50. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  51. ↑ 51.0 51.1 Lua error in package.lua at line 80: module 'strict' not found.
  52. ↑ 52.0 52.1 Lua error in package.lua at line 80: module 'strict' not found.
  53. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  54. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  55. ↑ 55.0 55.1 55.2 55.3 55.4 55.5 Lua error in package.lua at line 80: module 'strict' not found.
  56. ↑ 56.0 56.1 56.2 56.3 56.4 56.5 Lua error in package.lua at line 80: module 'strict' not found.
  57. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  58. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  59. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  60. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  61. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  62. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  63. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  64. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  65. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  66. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  67. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  68. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  69. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  70. ↑ 70.0 70.1 70.2 Lua error in package.lua at line 80: module 'strict' not found.
  71. ↑ Lua error in package.lua at line 80: module 'strict' not found.

Further reading

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External links

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