A cup of hot tea to welcome you!

Welcome to Wikiafripedia, the free encyclopedia that you can monetize your contributions. Aimed at WAP ZERO to the sum of all knowledge.
WAP is made by people like you, sign up and contribute.

A cup of hot tea to welcome you!

Welcome to Wikiafripedia, the free encyclopedia that you can monetize your contributions. Aimed at WAP ZERO to the sum of all knowledge.

WAP is made by people like you, sign up and contribute.

COVID-19 drug repurposing research

From Wikiafripedia, the free encyclopedia that you can monetize your contributions or browse at zero-rating.
Jump to navigation Jump to search

Drug repositioning (also known as drug re-purposing, re-profiling, re-tasking, or therapeutic switching) is the re-purposing 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 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]

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.[6][7][8]

In a statement to the journal Nature Biotechnology in February 2020, U.S. 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".[2]

RECOVERY Trial[edit source | edit]

A large-scale, randomized controlled trial named the RECOVERY Trial was set up in March 2020 in the U.K to test possible treatments for COVID-19. It is run by the Nuffield Departments of Public Health and of Medicine at the University of Oxford and is currently testing five repurposed drugs and also convalescent plasma. As of June 2020, the trial has enrolled more than 11,500 COVID-19 positive participants in the U.K.[9][10][11]

Studies[edit source | edit]

Chloroquine and hydroxychloroquine[edit source | edit]

U.S. President Donald Trump said he had been taking hydroxychloroquine.

Chloroquine is an anti-malarial medication also used against some auto-immune diseases. On 18 March, the World Health Organization (WHO) announced that chloroquine and the related hydroxychloroquine would be among the four drugs studied as part of the Solidarity clinical trial.[12] On 19 March, the U.S. 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 in the United States.[13] New York Governor Andrew Cuomo announced that New York State trials of chloroquine and hydroxychloroquine would begin on 24 March.[14]

On 28 March, the U.S. Food and Drug Administration (FDA) authorized the use of hydroxychloroquine sulfate and chloroquine phosphate under an Emergency Use Authorization (EUA).[15][16] The treatment has not been approved by the FDA's clinical trials process.[16] However, the drug is authorized under the EUA as an experimental treatment for emergency use in patients who are hospitalized, but are not able to receive treatment in a clinical trial.[16][17][15] The Centers for Disease Control and Prevention (CDC) said that "the use, dosing, or duration of hydroxychloroquine for prophylaxis or treatment of SARS-CoV-2 infection" are not yet established.[18] Doctors have said they are using the drug when "there's no other option".[19] 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.[19][20]

On 15 June 2020, the FDA revoked the emergency use authorization for hydroxychloroquine and chloroquine, stating that although the evaluation of both these drugs under clinical trials continues, the FDA (after interagency consultation with the Biomedical Advanced Research and Development Authority (BARDA)) concluded that, based on new information and other information discussed "... it is no longer reasonable to believe that oral formulations of hydroxychloroquine (HCQ) and chloroquine (CQ) may be effective in treating COVID‑19, nor is it reasonable to believe that the known and potential benefits of these products outweigh their known and potential risks".[21][22][23][24]

On 24 April, 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] According to Johns Hopkins' ABX Guide for COVID‑19, "Hydroxychloroquine 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".[26] Caution was also recommended as to the combination of chloroquine and hydroxychloroquine with treatments which might inhibit the CYP3A4 enzyme (by which these drugs are metabolized). As such, combination might indirectly result in higher plasma levels of chloroquine and hydroxychloroquine, and thus enhance the risk for significant QT prolongation. CYP3A4 inhibitors include Azithromycin, ritonavir and lopinavir.[27] A Veterans Affairs study released results on 21 April suggesting COVID‑19-hospitalized patients treated with hydroxychloroquine were more likely to die than those who received no drug treatment at all, after correcting for clinical characteristics.[28][29]

A chloroquine tablet

Drugs used for treatment of infectious diseases may also be considered for use for post-exposure prophylaxis. On 22 May, The Lancet published a response to criticism of the Indian government's decision to allow chemoprophylaxis with hydroxychloroquine for some high risk persons who may have had exposure to COVID. Researchers supporting prophylactic administration of hydroxychloquine note that results from recently published human trials have suggested that hydroxychloroquine may decrease the duration of both viral shedding and symptoms if the drug is administered early.[30] British researchers are studying whether the drug is effective when used for prevention. 10,000 National Health Service (NHS) workers, along with 30,000 additional volunteers from Asia, South America, Africa, and other parts of Europe are participating in the global study. Results are expected by the end of 2020.[31]

A randomized, double-blind, placebo-controlled trial of hydroxychloroquine in 821 participants by the University of Minnesota Medical School found that it does not treat COVID‑19 infection, but the study presented limitations.[32][33][34]

In June 2020, use of hydroxychloroquine in the UK RECOVERY Trial was discontinued when an interim analysis of 1,542 treatments showed it provided no mortality benefit to people hospitalized with severe COVID‑19 infection over 28 days of observation.[11]

Combined with zinc and another antibiotic[edit source | edit]

Due to the properties of zinc as a cofactor in the immune response for producing antibodies during viral infections,[35] it is being included among multiple-agent "cocktails" for investigating potential treatment of people hospitalized with COVID‑19 infection.[36] One such cocktail – hydroxychloroquine combined with a high dose of zinc (as a sulfate, 220 mg per day for five days, a zinc dose twenty times higher than the reference daily intake level)[35] and an approved antibiotic, either azithromycin or doxycycline – began in May as a Phase IV trial in New York State.[37] However, caution was recommended about the combination of chloroquine or hydroxychloroquine with CYP3A4 inhibitors, such as azithromycin,[27] a treatment combination found to be ineffective for preventing death in hospitalized people with COVID‑19.[38] There is preliminary evidence that combining hydroxychloroquine and azithromycin for treating non-hospitalized ("outpatient") people with COVID‑19 infection with multiple comorbidities was effective, but remains under preliminary research.[39]

Zinc deficiency – which decreases immune capacity to defend against pathogens – is common among elderly people, and may be a susceptibility factor in viral infections.[35] The mechanism for any potential benefit of including zinc in a cocktail treatment for recovery from severe COVID‑19 or any viral infection is unknown.[35][36]

Controversy[edit source | edit]

Due to safety concerns and evidence of heart arrhythmias leading to higher death rates, the WHO suspended the hydroxychloroquine arm of the multinational Solidarity trial in late May 2020.[40][41][42] The WHO had enrolled 3,500 patients from 17 countries in the Solidarity trial.[40] The research surrounding this suspension, provided by a company called Surgisphere based in Chicago, came into question due to errors in the underlying data set.[43][44][45] The authors of the study corrected errors in the data later but remained firm on their conclusions.[43]

The WHO decided to resume the trial on 3 June, after reviewing the safety concerns which had been raised. Speaking at a press briefing, WHO's director-general, Tedros Adhanom Ghebreyesus stated that the board had reviewed the available mortality data and had found "no reasons to modify the trial".[46][47]

A retraction of the study by three of its authors was published by The Lancet on 4 June, 2020.[48] The authors stated that their reason behind the retraction was because Surgisphere had failed to cooperate with an independent review of the data used for the study by not allowing any such review to take place.[49][50]

Dexamethasone[edit source | edit]

A vial of dexamethasone for injection

Dexamethasone is a corticosteroid medication currently in use for multiple conditions such as rheumatic problems, skin diseases, asthma and chronic obstructive lung disease among others.[51] A multi-center, randomized controlled trial of dexamethasone in treating acute respiratory distress syndrome (ARDS), published in February 2020, showed reduced need for mechanical ventilation and mortality.[52]

In June 2020, the Oxford University RECOVERY Trial announced and then published preliminary results that the drug could reduce deaths by about a third in participants on ventilators and by about a fifth in participants on oxygen.[53] Several experts have called for the full dataset to be published quickly to allow wider analysis of the results.[54][55] The World Health Organization (WHO) states that dexamethasone should be reserved for seriously ill and critical patients receiving COVID-19 treatment in a hospital setting.[56]

Demand for dexamethasone surges after publication of the preprint.[57]

Favipiravir[edit source | edit]

Chinese clinical trials in Wuhan and Shenzhen claimed to show that favipiravir was "clearly effective".[58] 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.[59] 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).[60]

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.[61] The Italian Medicines Agency reminded the public that the existing evidence in support of the drug is scant and preliminary.[62] 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.[63] According to the South China Morning Post, Shinzo Abe has made overtures to the Trump administration about purchasing the drug.[64]

The drug may be less effective in severe cases where the virus has already multiplied. It may not be safe for use by pregnant women or those trying to conceive.[59]

On 30 May 2020, the Russian Health Ministry approved a generic version of favipiravir named Avifavir, which proved highly effective in the first phase of clinical trials.[65][66][67]

Lopinavir / Ritonavir[edit source | edit]

One study of lopinavir/ritonavir (Kaletra), a combination of the antivirals lopinavir and ritonavir, concluded that "no benefit was observed".[68][69] 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.[70]

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.[12]

Remdesivir[edit source | edit]

Remdesivir was created and developed by Gilead Sciences as a treatment for Ebola virus disease and Marburg virus infections.[71]

During 2020, several clinical trials were underway.[7] 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.[72][73]

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.[74] 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.[75][74][76] 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.[74] 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.[74] The agreement between Gilead and five generic pharmaceutical companies in India and Pakistan will help make the medicine for 127 countries.[77] On 15 June 2020, the FDA updated the fact sheets for the emergency use authorization of remdesivir to warn that using chloroquine or hydroxychloroquine with remdesivir may reduce the antiviral activity of remdesivir.[78]

GS-441524[edit source | edit]

GS-441524 is the nucleoside of the phosphate pro-drug remdesivir. It has been shown to cure cats infected with Feline infectious peritonitis (FIP), a feline form of coronavirus with a 96% cure rate.[79] Studies have shown that even when remdesivir is administered, GS-441524 is the predominant metabolite circulating in serum due to rapid hydrolysis of the remdesivir pro-drugs, followed by dephosphorylation.[71][80][81][unreliable medical source?] Some researchers have suggested its utility as a treatment for COVID‑19.[82]

Vitamins[edit source | edit]

Intravenous vitamin C[edit source | edit]

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 and, U.S.) and three with no control (Italy, U.S. and, U.S.).[83]

Oral vitamin D[edit source | edit]

Oral vitamin D tablets

According to ClinicalTrials.gov, several Phase II–IV clinical trials are underway to assess the use of oral vitamin D for prevention or treatment of COVID‑19 infection, with most in preliminary stages and none completed, as of May 2020.[84] Most trials have the design of studying COVID‑19-infected people who are vitamin D deficient.[84] The rationale for these trials is based on speculation and observational reports that low vitamin D may be associated with a higher incidence and severity of this infection.[85] After adjustments were made for potential confounding factors, such as ethnicity, one study found insufficient evidence to indicate that vitamin D supplementation provided a benefit to reduce susceptibility to COVID‑19 infection.[86]

Other drugs[edit source | edit]

Drug Research
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.[87] A multicenter study on 300 patients researching the use of enoxaparin sodium at prophylaxis and therapeutic dosages was announced in Italy on 14 April.[88]
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.[89][90]
Artesunate/pyronaridine It was announced on 3 April 2020 that pyronaridine and artesunate, the main components of a new ACT antimalarial drug Pyramax[91], showed an inhibitory effect on SARS-COV-2 in vitro tests using Hela Cells. The Pyramax showed a virus titer inhibition rate of 99% or more after 24 hours, while cytotoxicity was also reduced[92]. However, no publication on in vitro test was made yet. Now, it is in phase II clinical trial, in South Korea.[93][94]
Azithromycin New York State began trials for the antibiotic azithromycin on 24 March 2020.[95]
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.[96]

Ciclesonide was identified as a candidate antiviral in an in vitro drug screening assay done in South Korea.[97]

Cimetidine Has been suggested as a treatment for COVID-19.[98][99]
Colchicine Researchers from the Montreal Heart Institute in Canada are studying the role of colchicine in reducing inflammation and pulmonary complications in patients suffering from mild symptoms of COVID‑19.[100] The study, named COLCORONA, is recruiting 6000 adults 40 and older who were diagnosed with COVID‑19 and experience mild symptoms not requiring hospitalization.[100][101] Women who are pregnant or breastfeeding or who do not have an effective contraceptive method are not eligible.[101]
Dipyridamole Is proposed as a treatment for COVID‑19,[98][99] and a clinical trial is underway.[102]
Famotidine Has been suggested as a treatment for COVID-19,[98][99][unreliable source?] and a clinical study is underway.[103]
Fibrates Fenofibrate and bezafibrate have been suggested for treatment of life-threatening symptoms of COVID-19.[98][99]
Ibuprofen A trial called "Liberate" has been started in the United Kingdom to determine the effectiveness of ibuprofen in reducing the severity and progression of lung injury which results in breathing difficulties for COVID‑19 patients. Subjects are to receive three doses of a special formulation of the drug – lipid ibuprofen – in addition to usual care.[104][105]
Interferon beta IFN-β will be included in the international Solidarity Trial in combination with the HIV drugs Lopinavir and Ritonavir.[106] as well as the REMAP-CAP[107]

Finnish biotech firm Faron Pharmaceuticals continues to develop INF-beta for ARDS and is involved in worldwide initiatives[which?] against COVID‑19, including the Solidarity trial.[108] UK biotech firm Synairgen started conducting trials on IFN-β, a drug that was originally developed to treat COPD.[12]

Mavrilimumab Is a human monoclonal antibody that inhibits human granulocyte macrophage colony-stimulating factor receptor (GM-CSF-R).[109][110] It has been studied to see if it can improve the prognosis for patients with COVID-19 pneumonia and systemic hyperinflammation. One small study indicated some beneficial effects of treatment with mavrilimumab compared with those who were not.[111]
nanoFenretinide nanoFenretinide is nanoparticle sized fenretinide and repurposed oncology drug approved to enter the clinic for a lymphoma indication.[112] It was identified as a candidate antiviral in an in vitro drug screening assay done in South Korea.[97] Fenretinide's clinical safety profile also makes it an ideal candidate in combination regimens.[citation needed]
Niclosamide It was identified as a candidate antiviral in an in vitro drug screening assay done in South Korea.[97]
Sildenafil Is proposed as a treatment for COVID-19,[98][99] and a Phase III clinical trial is underway.[113]
Tocilizumab In March 2020, China approved the drug for the treatment of inflammation in COVID-19 patients but found no conclusive evidence whether the treatment is effective.[114] The Australasian Society for Clinical Immunology and Allergy recommend tocilizumab be considered as an off-label treatment for those with COVID-19 related acute respiratory distress syndrome.[115]

It is part of the RECOVERY Trial in the UK to be tested as a potential treatment,[9] while Hoffmann–La Roche and the WHO have also launched separate trials for its use in severe cases.[116]

Drugs by class[edit source | edit]

Antibody[edit source | edit]

Antivirals[edit source | edit]

Considerable scientific attention has been focused on re-purposing approved antiviral drugs that have been previously developed against other viruses, such as MERS-CoV, SARS-CoV, and West Nile virus.[117]

Antiparasitics[edit source | edit]

Antibiotics[edit source | edit]

Some antibiotics that have been identified as potentially re-purposable as COVID‑19 treatments:[126][127]

Immunologicals[edit source | edit]

Drugs with immune modulating effects that may prove useful in COVID‑19 treatment:

References[edit source | edit]

  1. "Repurposing Drugs". National Center for Advancing Translational Sciences (NCATS). U.S. Department of Health & Human Services, National Institutes of Health. 7 November 2017. Retrieved 26 March 2020.
  2. 2.0 2.1 2.2 Harrison C (April 2020). "Coronavirus puts drug repurposing on the fast track". Nature Biotechnology. 38 (4): 379–381. doi:10.1038/d41587-020-00003-1. PMID 32205870.
  3. Sleigh SH, Barton CL (2010). "Repurposing Strategies for Therapeutics". Pharmaceutical Medicine. 24 (3): 151–159. doi:10.1007/BF03256811.
  4. "COVID-19 Vaccine Frontrunners".
  5. Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, et al. (April 2020). "Effectiveness of convalescent plasma therapy in severe COVID-19 patients". Proceedings of the National Academy of Sciences of the United States of America. 117 (17): 9490–9496. doi:10.1073/pnas.2004168117. PMC 7196837. PMID 32253318.
  6. Li G, De Clercq E (March 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.
  7. 7.0 7.1 "COVID-19 treatment and vaccines tracker (Choose tab of interest, apply filters to view select data)". Milken Institute. 2 June 2020. Retrieved 3 June 2020. Lay summary.
  8. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB (April 2020). "Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review". JAMA. doi:10.1001/jama.2020.6019. PMID 32282022.
  9. 9.0 9.1 9.2 "RECOVERY Trial". Retrieved 17 June 2020.
  10. Fergus Walsh (20 June 2020). "At last some good news about coronavirus". BBC News. Retrieved 20 June 2020.
  11. 11.0 11.1 "No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19". Recovery Trial, Nuffield Department of Population Health, University of Oxford, UK. 5 June 2020. Retrieved 7 June 2020.
  12. 12.0 12.1 12.2 Devlin H, Sample I (19 March 2020). "What are the prospects for a COVID-19 treatment?". The Guardian.
  13. Liu M, Caputi TL, Dredze M, Kesselheim AS, Ayers JW (April 2020). "Internet Searches for Unproven COVID-19 Therapies in the United States". JAMA Internal Medicine. doi:10.1001/jamainternmed.2020.1764. PMC 7191468. PMID 32347895.
  14. "NY COVID-19 cases surge; Javits Center to house temporary hospitals". Fox 5. 23 March 2020.
  15. 15.0 15.1 "Coronavirus (COVID-19) Update: Daily Roundup March 30, 2020" (Press release). U.S. Food and Drug Administration (FDA). 30 March 2020.
  16. 16.0 16.1 16.2 "Chloroquine phosphate and hydroxychloroquine sulfate for treatment of COVID-19 Emergency Use Authorization" (PDF). U.S. Food and Drug Administration (FDA). 28 March 2020. Retrieved 14 June 2020. This article incorporates text from this source, which is in the public domain.
  17. "Fact Sheet for Patients and Parent/Caregivers Emergency Use Authorization (EUA) of Chloroquine Phosphate for Treatment of COVID-19 in Certain Hospitalized Patients" (PDF). U.S. Food and Drug Administration (FDA).
  18. "Information for clinicians on therapeutic options for COVID-19 patients". U.S. Centers for Disease Control and Prevention. 21 March 2020. Retrieved 22 March 2020.
  19. 19.0 19.1 Gross SJ (9 April 2020). "As CDC drops guidance on chloroquine as COVID-19 therapy, doctors ask for research". Miami Herald.
  20. Clinical trial number NCT04332991 for "Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease (ORCHID)" at ClinicalTrials.gov
  21. "Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for Chloroquine and Hydroxychloroquine". U.S. Food and Drug Administration (FDA) (Press release). 15 June 2020. Retrieved 15 June 2020.
  22. "EUA Archive". U.S. Food and Drug Administration (FDA). 15 June 2020. Retrieved 15 June 2020. On June 15, 2020, based on FDA's continued review of the scientific evidence available for hydroxychloroquine sulfate (HCQ) and chloroquine phosphate (CQ) to treat COVID-19, FDA has determined that the statutory criteria for EUA as outlined in Section 564(c)(2) of the Food, Drug, and Cosmetic Act are no longer met. Specifically, FDA has determined that CQ and HCQ are unlikely to be effective in treating COVID-19 for the authorized uses in the EUA. Additionally, in light of ongoing serious cardiac adverse events and other serious side effects, the known and potential benefits of CQ and HCQ no longer outweigh the known and potential risks for the authorized use. This warrants revocation of the EUA for HCQ and CQ for the treatment of COVID-19. This article incorporates text from this source, which is in the public domain.
  23. "HCQ and CQ revocation letter" (PDF). U.S. Food and Drug Administration (FDA). 15 June 2020. Retrieved 15 June 2020. This article incorporates text from this source, which is in the public domain.
  24. "Frequently Asked Questions on the Revocation of the Emergency Use Authorization for Hydroxychloroquine Sulfate and Chloroquine Phosphate" (PDF). U.S. Food and Drug Administration (FDA). 15 June 2020. Retrieved 15 June 2020.
  25. "FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems". U.S. Food and Drug Administration (FDA). 24 April 2020. Retrieved 1 May 2020.
  26. see under Treatment section of Coronavirus COVID‑19 (SARS-CoV-2); Johns Hopkins ABX Guide (Retrieved 18 April 2020)
  27. 27.0 27.1 Wu CI, Postema PG, Arbelo E, Behr ER, Bezzina CR, Napolitano C, et al. (March 2020). "SARS-CoV-2, COVID-19, and inherited arrhythmia syndromes". Heart Rhythm. doi:10.1016/j.hrthm.2020.03.024. PMC 7156157. PMID 32244059.
  28. Rowland, Christopher. "Anti-malarial drug Trump touted is linked to higher rates of death in VA coronavirus patients, study says". The Washington Post. Retrieved 22 April 2020.
  29. Magagnoli J, Narendran S, Pereira F, Cummings TH, Hardin JW, Sutton SS, et al. (5 June 2020). "Outcomes of hydroxychloroquine usage in United States veterans hospitalized with COVID-19". Med. Lay summary.
  30. Tilangi P, Desai D, Khan A, Soneja M (May 2020). "Hydroxychloroquine prophylaxis for high-risk COVID-19 contacts in India: a prudent approach". The Lancet. Infectious Diseases. doi:10.1016/S1473-3099(20)30430-8. PMC 7255125. PMID 32450054.
  31. "Hydroxychloroquine: NHS staff to take drug as part of global trial". The Guardian. 21 May 2020.
  32. Boulware DR, Pullen MF, Bangdiwala AS, Pastick KA, Lofgren SM, Okafor EC, et al. (June 2020). "A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19". The New England Journal of Medicine. doi:10.1056/NEJMoa2016638. PMID 32492293. Lay summary.
  33. Cohen MS (June 2020). "Hydroxychloroquine for the Prevention of Covid-19 – Searching for Evidence". The New England Journal of Medicine. doi:10.1056/NEJMe2020388. PMID 32492298.
  34. Laurie McGinley; Ariana Eunjung Cha (3 June 2020). "Hydroxychloroquine, a drug promoted by Trump, failed to prevent healthy people from getting covid-19 in trial". The Washington Post. Retrieved 5 June 2020.
  35. 35.0 35.1 35.2 35.3 "Zinc". Micronutrient Information Center, Linus Pauling Institute, Oregon State University. 1 May 2019. Retrieved 20 May 2020.
  36. 36.0 36.1 Brian P. Dunleavy (13 May 2020). "Zinc might boost effectiveness of malaria drug against COVID-19, experts say". United Press International. Retrieved 20 May 2020.
  37. Clinical trial number NCT04370782 for "Hydroxychloroquine and Zinc With Either Azithromycin or Doxycycline for Treatment of COVID-19 in Outpatient Setting" at ClinicalTrials.gov
  38. Rosenberg ES, Dufort EM, Udo T, Wilberschied LA, Kumar J, Tesoriero J, et al. (May 2020). "Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State". JAMA. doi:10.1001/jama.2020.8630. PMC 7215635. PMID 32392282.
  39. Risch HA (May 2020). "Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis". American Journal of Epidemiology: kwaa093. doi:10.1093/aje/kwaa093. PMID 32458969.
  40. 40.0 40.1 "WHO Director-General's opening remarks at the media briefing on COVID-19 – 25 May 2020". World Health Organization. 25 May 2020. Retrieved 27 May 2020.
  41. Maria Cheng, Jamey Keaten (25 May 2020). "WHO pauses hydroxychloroquine coronavirus trial over safety concerns". Global News. The Associated Press. Retrieved 27 May 2020.CS1 maint: uses authors parameter (link)
  42. "Coronavirus: WHO halts trials of hydroxychloroquine over safety fears". BBC News Online. 25 May 2020. Retrieved 4 June 2020.
  43. 43.0 43.1 Matthew Herper; Andrew Joseph (2 June 2020). "Top medical journals raise concerns about data in two studies related to Covid-19". Stat. Retrieved 4 June 2020.
  44. "A mysterious company's coronavirus papers in top medical journals may be unraveling". AAAS. AAAS. 3 June 2020. Retrieved 3 June 2020.
  45. Melissa Davey (28 May 2020). "Questions raised over hydroxychloroquine study which caused WHO to halt trials for Covid-19". The Guardian. Retrieved 4 June 2020.
  46. Andrew Joseph (3 June 2020). "WHO resumes hydroxychloroquine study for Covid-19, after reviewing safety concerns". Stat. Retrieved 4 June 2020.
  47. Shaun Lintern (3 June 2020). "Coronavirus: WHO re-starts hydroxychloroquine trials amid controversy over published research". The Independent. Retrieved 4 June 2020.
  48. Mehra MR, Ruschitzka F, Patel AN (4 June 2020). "Retraction: "Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis"". The Lancet. doi:10.1016/S0140-6736(20)31324-6 (inactive 5 June 2020).CS1 maint: DOI inactive as of June 2020 (link)
  49. "Coronavirus: Influential study on hydroxychloroquine withdrawn". BBC News Online. 5 June 2020. Retrieved 5 June 2020.
  50. Boseley S, Davey M (4 June 2020). "Covid-19: Lancet retracts paper that halted hydroxychloroquine trials". The Guardian. Retrieved 4 June 2020.
  51. "Dexamethasone". The American Society of Health-System Pharmacists. Archived from the original on 31 August 2017. Retrieved 29 July 2015.
  52. Villar, Jesús; Ferrando, Carlos; Martínez, Domingo; Ambrós, Alfonso; Muñoz, Tomás; Soler, Juan A; et al. (2020). "Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial". The Lancet Respiratory Medicine. 8 (3): 267–276. doi:10.1016/s2213-2600(19)30417-5. ISSN 2213-2600. Early administration of dexamethasone could reduce duration of mechanical ventilation and overall mortality in patients with established moderate-to-severe ARDS.
  53. "Dexamethasone reduces death in hospitalised patients with severe respiratory complications of COVID-19". University of Oxford. 16 June 2020. Retrieved 16 June 2020.
  54. "Steroid drug hailed as 'breakthrough' for seriously ill COVID-19 patients". Reuters. 17 June 2020. Retrieved 18 June 2020.
  55. Ducharme, Jamie. "A Low-Cost Steroid Shows Promise for Treating COVID-19. But Take the News With a Grain of Salt". Time. Retrieved 18 June 2020.
  56. "Important to use dexamethasone only for serious COVID cases - WHO". 17 June 2020. Retrieved 18 June 2020.
  57. Covid-19: Demand for dexamethasone surges as RECOVERY trial publishes preprint BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m2512
  58. McCurry J (18 March 2020). "Japanese flu drug 'clearly effective' in treating coronavirus, says China".
  59. 59.0 59.1 Gregory A (18 March 2020). "Coronavirus: Japanese anti-viral drug effective in treating patients, Chinese official says". The Independent.
  60. Regalado A (23 March 2020). "Which Covid-19 drugs work best?". MIT Technology Review.
  61. di Pietrobelli G (22 March 2020). "Coronavirus, il Veneto sperimenta l'antivirale giapponese Favipiravir. Ma l'Aifa: "Ci sono scarse evidenze scientifiche su efficacia"". Il Fatto Quotidiano (in Italian). Retrieved 23 March 2020.
  62. "AIFA precisa, uso favipiravir per COVID-19 non autorizzato in Europa e USA, scarse evidenze scientifiche sull'efficacia". aifa.gov.it (in Italian). 22 March 2020. Retrieved 23 March 2020.
  63. Fukao K (3 April 2020). "Berlin to stockpile millions of doses of Fujifilm's anti-flu drug". Nikkei Asian Review.
  64. Jeong-ho L. "China and South Korea split over Japanese anti-flu drug Avigan in fight against coronavirus". South China Morning Post.
  65. "Russian Ministry of Health approves the first COVID-19 drug Avifavir produced by JV of RDIF and ChemRar". RDIF. 30 May 2020. Retrieved 31 May 2020.
  66. "Russian Health Ministry approves anti-coronavirus drug Avifavir". BNN Bloomberg. 31 May 2020. Retrieved 31 May 2020.
  67. "Russia plans coronavirus vaccine clinical trials in two weeks – report". Reuters. 30 May 2020. Retrieved 31 May 2020.
  68. "Antiviral Drug Combo Ineffective Vs. Coronavirus". WebMD. 20 March 2020.
  69. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. (May 2020). "A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19". The New England Journal of Medicine. 382 (19): 1787–1799. doi:10.1056/NEJMoa2001282. PMC 7121492. PMID 32187464.
  70. Brown J (20 March 2020). "Colorado researchers are racing to find an antiviral drug that could save people with the new coronavirus".
  71. 71.0 71.1 Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, Soloveva V, et al. (March 2016). "Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys". Nature. 531 (7594): 381–5. Bibcode:2016Natur.531..381W. doi:10.1038/nature17180. PMC 5551389. PMID 26934220.
  72. 72.0 72.1 Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. (May 2020). "Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial". Lancet. 395 (10236): 1569–1578. doi:10.1016/S0140-6736(20)31022-9. PMC 7190303. PMID 32423584.
  73. Boseley S (23 April 2020). "First trial for potential Covid-19 drug shows it has no effect". The Guardian. ISSN 0261-3077. Retrieved 25 April 2020.
  74. 74.0 74.1 74.2 74.3 "Frequently Asked Questions on the Emergency Use Authorization for Remdesivir for Certain Hospitalized COVID‐19 Patients" (PDF). U.S. Food and Drug Administration (FDA). 1 May 2020. Retrieved 1 May 2020. This article incorporates text from this source, which is in the public domain.
  75. "Emergency Use Authorization (EUA) of Remdesivir for Coronavirus Disease 2019 (COVID-19)" (PDF). U.S. Food and Drug Administration (FDA). 1 May 2020. Retrieved 1 May 2020. Lay summary. This article incorporates text from this source, which is in the public domain.
  76. Holland S, Mason J, Maler S (1 May 2020). "FDA Authorizes Remdesivir Drug for COVID-19". The New York Times.
  77. Silverman, Ed (12 May 2020). "Gilead signs deals for generic companies to make and sell remdesivir". Stat. Retrieved 30 May 2020.
  78. "Coronavirus (COVID-19) Update: FDA Warns of Newly Discovered Potential Drug Interaction That May Reduce Effectiveness of a COVID-19 Treatment Authorized for Emergency Use". U.S. Food and Drug Administration (FDA) (Press release). 15 June 2020. Retrieved 15 June 2020. This article incorporates text from this source, which is in the public domain.
  79. Pedersen NC, Perron M, Bannasch M, Montgomery E, Murakami E, Liepnieks M, Liu H (April 2019). "Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis". Journal of Feline Medicine and Surgery. 21 (4): 271–281. doi:10.1177/1098612X19825701. PMC 6435921. PMID 30755068.
  80. Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, et al. (June 2017). "Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses". Science Translational Medicine. 9 (396): eaal3653. doi:10.1126/scitranslmed.aal3653. PMC 5567817. PMID 28659436.
  81. Williamson, Brandi N.; Feldmann, Friederike; Schwarz, Benjamin; Meade-White, Kimberly; Porter, Danielle P.; Schulz, Jonathan; Doremalen, Neeltje van; Leighton, Ian; Yinda, Claude Kwe; Pérez-Pérez, Lizzette; Okumura, Atsushi; Lovaglio, Jamie; Hanley, Patrick W.; Saturday, Greg; Bosio, Catharine M.; Anzick, Sarah; Barbian, Kent; Cihlar, Tomas; Martens, Craig; Scott, Dana P.; Munster, Vincent J.; Wit, Emmie de (22 April 2020). "Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2". bioRxiv: 2020.04.15.043166. doi:10.1101/2020.04.15.043166.
  82. "Gilead should ditch remdesivir and focus on its simpler ancestor". Stat. 14 May 2020. Retrieved 5 June 2020.
  83. "clinicaltrials.gov Vitamin C COVID-19". 26 March 2020. Retrieved 28 April 2020.
  84. 84.0 84.1 "International clinical trials assessing vitamin D in people with COVID-19". ClinicalTrials.gov, U.S. National Library of Medicine. May 2020. Retrieved 20 May 2020.
  85. Rhodes JM, Subramanian S, Laird E, Kenny RA (June 2020). "Editorial: low population mortality from COVID-19 in countries south of latitude 35 degrees North supports vitamin D as a factor determining severity". Alimentary Pharmacology & Therapeutics. 51 (12): 1434–1437. doi:10.1111/apt.15777. PMC 7264531. PMID 32311755.
  86. Hastie CE, Mackay DF, Ho F, Celis-Morales CA, Katikireddi SV, Niedzwiedz CL, et al. (May 2020). "Vitamin D concentrations and COVID-19 infection in UK Biobank". Diabetes & Metabolic Syndrome. 14 (4): 561–565. doi:10.1016/j.dsx.2020.04.050. PMC 7204679. PMID 32413819.
  87. "Farmaci utilizzabili per il trattamento della malattia COVID19 | Agenzia Italiana del Farmaco". aifa.gov.it (in Italian). Retrieved 15 April 2020.
  88. "Coronavirus, al via studio su eparina per 300 pazienti". Adnkronos. Retrieved 15 April 2020.
  89. Ansede M (3 April 2020). "Doscientos enfermos probarán un fármaco que ha bloqueado el coronavirus en minirriñones humanos". El País (in Spanish). Retrieved 3 April 2020.
  90. "Apeiron Biologics moves forward with APN01 for treatment of COVID-19". www.thepharmaletter.com. Retrieved 3 April 2020.
  91. "Pyramax® (pyronaridine-artesunate)". www.mmv.org. Retrieved 26 June 2020.
  92. "'Pyramax' drug repurposing?... targets COVID-19 treatment". Doctor's News. Retrieved 25 June 2020.
  93. "COVID-19: Pyramax Enters Phase II Clinical Trial in South Korea". www.pharmanewsonline.com. Retrieved 17 June 2020.
  94. "A Multi-center, Randomized, Double-blind, Parallel, Placebo-Controlled, Phase Ⅱ Clinical Trial to Evaluate Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients". nedrug.mfds.go.kr. Retrieved 25 June 2020.
  95. 95.0 95.1 "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.
  96. "Japan Plans Alvesco Clinical Trial for Coronavirus". pj.jiho.jp. 31 March 2020.
  97. 97.0 97.1 97.2 Jeon S, Ko M, Lee J, Choi I, Byun SY, Park S, et al. (May 2020). "Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs". Antimicrobial Agents and Chemotherapy. American Society for Microbiology. doi:10.1128/aac.00819-20. PMID 32366720. Lay summary. Drug repositioning is the only feasible option to address the COVID‑19 global challenge immediately. We screened a panel of 48 FDA-approved drugs against SARS-CoV-2 which were pre-selected by an assay of SARS-CoV and identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low micromolar IC50s and in particular, two FDA-approved drugs – niclosamide and ciclesonide – were notable in some respects.
  98. 98.0 98.1 98.2 98.3 98.4 Rogosnitzky M, Berkowitz E, Jadad AR (May 2020). "Delivering Benefits at Speed Through Real-World Repurposing of Off-Patent Drugs: The COVID-19 Pandemic as a Case in Point". JMIR Public Health and Surveillance. 6 (2): e19199. doi:10.2196/19199. PMC 7224168. PMID 32374264.
  99. 99.0 99.1 99.2 99.3 99.4 Rogosnitzky M, Berkowitz E, Jadad AR. "Real-world Repurposing of Generic Drugs as a Multifaceted Strategy against COVID-19 JMIR Preprints. 23/04/2020:19583". doi:10.2196/preprints.19583. Cite journal requires |journal= (help)
  100. 100.0 100.1 ICI.Radio-Canada.ca, Zone Santé-. "Début d'une étude clinique pour tester un médicament contre les effets de la COVID-19 | Coronavirus". Radio-Canada.ca.
  101. 101.0 101.1 "COLCORONA Clinical Trial | Stop COVID-19". Colcorona.
  102. "Chinese Clinical Trial Register (ChiCTR) – The world health organization international clinical trials registered organization registered platform". www.chictr.org.cn.
  103. "New York clinical trial quietly tests heartburn remedy against coronavirus". Science. 26 April 2020.
  104. "LIBERATE Trial in COVID-19 (LIBERATE)". U.S. National Library of Medicine. 6 April 2020. Retrieved 4 June 2020.
  105. "Coronavirus: Ibuprofen tested as a treatment". BBC. 3 June 2020. Retrieved 4 June 2020.
  106. 106.0 106.1 "WHO officials enroll first patients from Norway and Spain in 'historic' coronavirus drug trial". CNBC. 27 March 2020.
  107. 107.0 107.1 "REMAP-CAP Trial". REMAP-CAP.
  108. "Traumakine to be a part of WHO's Solidarity trial investigating potential COVID-19 treatments". Faron Pharmaceuticals (Press release). 27 April 2020. Retrieved 8 May 2020.
  109. "Statement On A Nonproprietary Name Adopted By The USAN Council: Mavrilimumab" (PDF). American Medical Association. Archived from the original (PDF) on 28 September 2012.
  110. Burmester GR, Feist E, Sleeman MA, Wang B, White B, Magrini F (September 2011). "Mavrilimumab, a human monoclonal antibody targeting GM-CSF receptor-α, in subjects with rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase I, first-in-human study". Annals of the Rheumatic Diseases. 70 (9): 1542–9. doi:10.1136/ard.2010.146225. PMC 3147227. PMID 21613310.
  111. 111.0 111.1 De Luca G, Cavalli G, Campochiaro C, Della-Torre E, Angelillo P, Tomelleri A, et al. (16 June 2020). "GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study". The Lancet Rheumatology. doi:10.1016/S2665-9913(20)30170-3.
  112. "Phase 1 Trial of ST-001 nanoFenretinide in Relapsed/Refractory T-cell Non-Hodgkin Lymphoma – Full Text View – ClinicalTrials.gov". clinicaltrials.gov.
  113. "A Pilot Study of Sildenafil in COVID-19 – Full Text View – ClinicalTrials.gov". clinicaltrials.gov.
  114. "China approves use of Roche arthritis drug for coronavirus patients". Reuters. 4 March 2020.
  115. Grainger, Suzanne. "ASCIA Position Statement: Specific Treatments for COVID-19". Australasian Society of Clinical Immunology and Allergy (ASCIA). Retrieved 2 May 2020.
  116. "WHO and Roche launch trials of potential coronavirus treatments". SwissInfo.Ch.
  117. Dong L, Hu S, Gao J (2020). "Discovering drugs to treat coronavirus disease 2019 (COVID-19)". Drug Discoveries & Therapeutics. 14 (1): 58–60. doi:10.5582/ddt.2020.01012. PMID 32147628.
  118. Dong L, Hu S, Gao J (29 February 2020). "Discovering drugs to treat coronavirus disease 2019 (COVID-19)". Drug Discoveries & Therapeutics. 14 (1): 58–60. doi:10.5582/ddt.2020.01012. PMID 32147628.
  119. Lu H (March 2020). "Drug treatment options for the 2019-new coronavirus (2019-nCoV)". Bioscience Trends. 14 (1): 69–71. doi:10.5582/bst.2020.01020. PMID 31996494.
  120. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. (March 2020). "Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro". Cell Research. 30 (3): 269–271. doi:10.1038/s41422-020-0282-0. PMC 7054408. PMID 32020029.
  121. Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. (March 2020). "Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial". International Journal of Antimicrobial Agents: 105949. doi:10.1016/j.ijantimicag.2020.105949. PMC 7102549. PMID 32205204.
  122. Weston S, Haupt R, Logue J, Matthews K, Frieman MB (27 March 2020). "FDA approved drugs with broad anti-coronaviral activity inhibit SARS-CoV-2 in vitro". bioRxiv. doi:10.1101/2020.03.25.008482.
  123. "ФМБА России: доказана противовирусная активность "Мефлохина" в отношении возбудителя COVID-19". fmbaros.ru (in Russian). Federal Biomedical Agency. 10 April 2020. Retrieved 11 April 2020.
  124. Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM (April 2020). "The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro". Antiviral Research. 178: 104787. doi:10.1016/j.antiviral.2020.104787. PMC 7129059. PMID 32251768.
  125. Clinical trial number NCT04339426 for "Atovaquone and Azithromycin Combination for Confirmed COVID-19 Infection" at ClinicalTrials.gov
  126. "Coronavirus: Scientists could repurpose drugs to treat infection". Medical News Today. Retrieved 20 March 2020.
  127. "Existing Drugs May Offer a First-Line Treatment for Coronavirus Outbreak". Global Health News Wire. Retrieved 20 March 2020.
  128. Baron SA, Devaux C, Colson P, Raoult D, Rolain JM (April 2020). "Teicoplanin: an alternative drug for the treatment of COVID-19?". International Journal of Antimicrobial Agents. 55 (4): 105944. doi:10.1016/j.ijantimicag.2020.105944. PMC 7102624. PMID 32179150.
  129. 129.0 129.1 129.2 Andersen PI, Ianevski A, Lysvand H, Vitkauskiene A, Oksenych V, Bjørås M, et al. (April 2020). "Discovery and development of safe-in-man broad-spectrum antiviral agents". International Journal of Infectious Diseases. 93: 268–276. doi:10.1016/j.ijid.2020.02.018. PMC 7128205. PMID 32081774.

Further reading[edit source | edit]

External links[edit source | edit]

"COVID-19 therapeutics tracker". Regulatory Affairs Professionals Society.