COVID-19 drug repurposing research

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]

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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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, have been researched as potential COVID‑19 treatments, with some moving into clinical trials.[6][7][8]

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".[2]

RECOVERY Trial
Main article: RECOVERY Trial

A large-scale, randomized controlled trial named the RECOVERY Trial was set up in March 2020, in the UK 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 testing five repurposed drugs and also convalescent plasma. The trial enrolled more than 11,500 COVID-19 positive participants in the U.K by June 2020.[9][10][11]

By the end of June 2020, the trial had published findings regarding hydroxychloroquine and dexamethasone.[11][12] It had also announced results for lopinavir/ritonavir which were published in October 2020. The lopinavir-ritonavir and hydroxychloroquine arms were closed to new entrants after being shown to be ineffective.[13][11][14] Dexamethasone was closed to new adult entries after positive results and by November 2020, was open to child entries.

Studies

Chloroquine and hydroxychloroquine
See also: Chloroquine § COVID-19, and Hydroxychloroquine § COVID-19

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 multinational Solidarity clinical trial.[15]

On 19 March, US 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.[16] New York Governor Andrew Cuomo announced that New York State trials of chloroquine and hydroxychloroquine would begin on 24 March.[17] On 28 March, the US Food and Drug Administration (FDA) authorized the use of hydroxychloroquine sulfate and chloroquine phosphate under an Emergency Use Authorization (EUA), which was later revoked due to the risk of cardiac adverse events.[18][19] The drug was authorized under the EUA as an experimental treatment for emergency use in hospitalized patients.[19][20][18]

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.[21][22] 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.[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]

On 5 June, 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]

On 15 June, 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".[28][29][30][31]

A chloroquine tablet

On 23 July, results were published from a multicenter, randomized, open-label, three-group, controlled trial of 667 participants in Brazil which found no benefit from using hydroxychloroquine, alone or with azithromycin, to treat mild-to-moderate COVID‑19.[32] In July, the U.S President Donald Trump once again promoted the use of the drug contradicting various public health officials, including National Institute of Allergy and Infectious Diseases director Dr. Anthony Fauci.[33]

In November 2020, a US National Institutes of Health clinical trial evaluating the safety and effectiveness of hydroxychloroquine for the treatment of adults with COVID-19 formally concluded that the drug provided no clinical benefit to hospitalized patients.[34][35]

Combined with zinc and another antibiotic

Due to the properties of zinc as a cofactor in the immune response for producing antibodies during viral infections,[36] it is being included among multiple-agent "cocktails" for investigating potential treatment of people hospitalized with COVID‑19 infection.[37] One such cocktail – hydroxychloroquine combined with a high dose of zinc (as a sulfate, 220 mg (50 mg elemental Zn) per day for five days, a zinc dose ~4 times higher than the reference daily intake level)[36] and an approved antibiotic, either azithromycin or doxycycline – began in May as a Phase IV trial in New York State.[38] 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.[39] 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.[40]

Zinc deficiency – which decreases immune capacity to defend against pathogens – is common among elderly people, and may be a susceptibility factor in viral infections.[36] 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.[36][37]

Prophylaxis

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 human trials have suggested that hydroxychloroquine may decrease the duration of both viral shedding and symptoms if the drug is administered early.[41]

On 3 June, results were published from a randomized, double-blind, placebo-controlled trial of 821 participants which found that hydroxychloroquine did not prevent symptomatic COVID-19 illness when used for post-exposure prophylaxis.[42][43][44]

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.[45]

Controversy
See also: Surgisphere § COVID-19 controversy

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 May 2020.[46][47][48] The WHO had enrolled 3,500 patients from 17 countries in the Solidarity trial.[46] 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.[49][50][51] The authors of the study corrected errors in the data later but initially remained firm on their conclusions.[49] Subsequently, a retraction of the study by three of its authors was published by The Lancet on 4 June, 2020.[52] 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.[53][54]

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".[55][56]

On 4 July, the WHO discontinued the hydroxychloroquine trial based on evidence presented at the July WHO Summit on COVID-19 research and innovation. The WHO stated that "the interim results do not provide solid evidence of increased mortality was interrupted when interim results did not find significant mortality reduction in hospitalized patients.[57]

Dexamethasone
See also: Dexamethasone § COVID-19
A vial of dexamethasone for injection

Dexamethasone is a corticosteroid medication in use for multiple conditions such as rheumatic problems, skin diseases, asthma and chronic obstructive lung disease among others.[58] 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.[59]

On 16 June, the Oxford University RECOVERY Trial issued a press release announcing 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; it did not benefit patients who did not require respiratory support. The researchers estimated that treating 8 patients on ventilators with dexamethasone saved one life, and treating 25 patients on oxygen saved one life.[12] Several experts called for the full dataset to be published quickly to allow wider analysis of the results.[60][61] A preprint was published on June 22[62] and the peer-reviewed article appeared on July 17.[63]

Based on those preliminary results, dexamethasone treatment has been recommended by the US National Institutes of Health (NIH) for patients with COVID-19 who are mechanically ventilated or who require supplemental oxygen but are not mechanically ventilated. The NIH recommends against using dexamethasone in patients with COVID-19 who do not require supplemental oxygen.[64] In July 2020, the World Health Organization (WHO) stated they are in the process of updating treatment guidelines to include dexamethasone or other steroids.[65]

The Infectious Diseases Society of America (IDSA) guideline panel suggests the use of glucocorticoids for patients with severe COVID-19; where severe is defined as patients with oxygen saturation (SpO2) ≤94% on room air, and those who require supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).[66] The IDSA recommends against the use of glucocorticoids for those with COVID-19 without hypoxemia requiring supplemental oxygen.[66]

In July 2020, the European Medicines Agency (EMA) started reviewing results from the RECOVERY study arm that involved the use of dexamethasone in the treatment of patients with COVID-19 admitted to the hospital to provide an opinion on the results. It focused particularly on the potential use of the drug for the treatment of adults with COVID-19.[67]

In September 2020, the WHO released updated guidance on using corticosteroids for COVID-19.[68] The WHO recommends systemic corticosteroids rather than no systemic corticosteroids for the treatment of people with severe and critical COVID-19 (strong recommendation, based on moderate certainty evidence).[68] The WHO suggests not to use corticosteroids in the treatment of people with non-severe COVID-19 (conditional recommendation, based on low certainty evidence).[68]

In September 2020, the European Medicines Agency (EMA) endorsed the use of dexamethasone in adults and adolescents (from twelve years of age and weighing at least 40 kg) who require supplemental oxygen therapy.[69] Dexamethasone can be taken by mouth or given as an injection or infusion (drip) into a vein.[69]

Favipiravir
See also: Favipiravir § COVID-19

Favipiravir is an antiviral drug approved for the treatment of influenza in Japan.[70]

There is limited evidence suggesting that, compared to other antiviral drugs, favipiravir might improve outcomes for people with COVID-19, but more rigorous studies are needed before any conclusions can be drawn.[71]

Ivermectin

In vitro, ivermectin has antiviral effects against several distinct positive-sense single-strand RNA viruses, including SARS-CoV-2.[72] This has made it an attractive target for COVID-19 drug repurposing research. Subsequent studies found that ivermectin could inhibit replication of SARS-CoV-2 in monkey kidney cell culture with an IC50 of 2.2–2.8 µM.[73][74] Based on these data, however, doses much higher than the maximum approved or safely achievable for use in humans would be required for an antiviral effect.[75] Aside from practical difficulties, such high doses are not covered by current human-use approvals of the drug and would be toxic, as the antiviral mechanism of action is considered to operate via the suppression of a host cellular process,[75] specifically the inhibition of nuclear transport by importin α/β1.[76]

In November 2020, a systematic review found weak evidence of benefit when ivermectin is used as an add-on therapy for people with non-severe COVID-19.[77] A randomized controlled trial (RCT) of 24 patients with non-severe COVID-19 and no risk factors found no difference in PCR-positive nasal swabs nor in viral load between patients who received ivermectin and those given placebo, thus failing the primary outcome of the study.[78] Merck, the company from which the drug originated, has said that there is no good evidence ivermectin is plausible or effective as a drug used against COVID-19, and that attempting such use may be unsafe.[79]

As of January 2021, the U.S. National Institutes of Health COVID-19 Treatment Guidelines state that the evidence for ivermectin is too limited to allow for a recommendation for or against its use.[80] Ivermectin is not approved by the FDA for anti-viral use.[80] Additional evidence from RCTs and dose-response studies are needed.[81] At least 45 such trials were listed as of January 2021.[78]

It was reported in June 2020 that despite the absence of high-quality evidence to suggest any efficacy, use of ivermectin for prevention or treatment of early-stage COVID-19 has become increasingly widespread especially in Latin America, raising concerns about self-medication, safety, and the feasibility of future clinical trials.[82][83] In response, the Brazilian Health Regulatory Agency, Brazilian Society of Infectious Diseases, and Brazilian Thoracic Society all issued position statements in July[84] or January 2021[85][86] advising against the use of ivermectin for this purpose, and the government of Peru rescinded a previous recommendation for the use of ivermectin (alongside azithromycin and hydroxychloroquine) in hospitalized patients,[87] although as of January 2021 it is still prescribed for outpatient use.[88]

Lopinavir/ritonavir

One study of lopinavir/ritonavir (Kaletra), a combination of the antivirals lopinavir and ritonavir, concluded that "no benefit was observed".[89][90] 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.[91] There are criticisms within the scientific community about directing resources to repurposing drugs specifically developed for HIV/AIDS because such drugs are unlikely to be effective against a virus lacking the specific HIV-1 protease they target.[2] The WHO included lopinavir/ritonavir in the international Solidarity trial.[15]

On 29 June, the chief investigators of the UK RECOVERY Trial reported that there was no clinical benefit from use of lopinavir-ritonavir in 1,596 people hospitalized with severe COVID-19 infection over 28 days of treatment.[13][14]

A study published in October 2020 screening those FDA approved drugs which target SARS-CoV-2 spike (S) protein proposed that the current unbalanced combination formula of lopinavir might in fact interfere with the ritonavir's blocking activity on the receptor binding domain-human angiotensin converting enzyme-2 (RBD-hACE2) interaction, thus effectively limiting its therapeutic benefit in COVID-19 cases.[92]

Remdesivir
See also: Remdesivir § COVID-19

Remdesivir was created and developed by Gilead Sciences as a treatment for hepatitis C,[93] and was subsequently repurposed for Ebola virus disease and Marburg virus infections.[94]

In November 2020, the World Health Organization updated its guideline on therapeutics for COVID-19 to include a conditional recommendation against the use of remdesivir, triggered by results from the WHO Solidarity trial.[95][96]

The Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) on May 1, 2020 to allow the use of Remdesivir for the treatment of suspected or laboratory-confirmed COVID-19 in adult and pediatric patients hospitalized with severe disease.[97] On August 28 the scope of the EUA was expanded to a broader hospitalized population. The FDA approved Remdesivir for use in adults and pediatric patients on October 22 for the treatment of COVID-19 requiring hospitalization.[98]

Remdesivir/baricitinib

In May 2020, the National Institute of Allergy and Infectious Diseases (NIAID) started the Adaptive COVID-19 Treatment Trial 2 (ACTT-2) to evaluate the safety and efficacy of a treatment regimen consisting of remdesivir plus baricitinib for treating hospitalized adults who have a laboratory-confirmed SARS-CoV-2 infection with evidence of lung involvement, including a need for supplemental oxygen, abnormal chest X-rays, or illness requiring mechanical ventilation.[99][100][101]

In November 2020, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for the drug baricitinib, in combination with remdesivir, for the treatment of suspected or laboratory confirmed COVID-19 in hospitalized people two years of age or older requiring supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).[102] The data supporting the EUA for baricitinib combined with remdesivir are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), which was conducted by the National Institute of Allergy and Infectious Diseases (NIAID).[102] The EUA was issued to Eli Lilly and Company.[102]

Remdesivir/interferon beta-1a

In August 2020, the NIAID started the Adaptive COVID-19 Treatment Trial 3 (ACTT 3) to evaluate the safety and efficacy of a treatment regimen consisting of remdesivir plus interferon beta-1a for hospitalized adults who have a laboratory-confirmed SARS-CoV-2 infection with evidence of lung involvement, including a need for supplemental oxygen, abnormal chest X-rays, or illness requiring mechanical ventilation.[100][103]

GS-441524

GS-441524 is the nucleoside of the ProTide remdesivir. It has been shown to cure cats infected with Feline infectious peritonitis (FIP), a feline form of coronavirus with a 96% cure rate.[104][105] 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.[106][94][107][108] Some researchers have suggested its utility as a treatment for COVID‑19,[109][110][111][112][113] noting easier synthesis, lack of first-pass metabolism in the liver, greater hydrophilicity and triphosphate formation in cell types irrespective of expression CES1 and CTSA, the enzymes required to bioactivate remdesivir.

Tocilizumab

Tocilizumab is an interleukin 6 inhibitor authorized for use in several conditions, including rheumatoid arthritis, giant cell arteritis, systemic juvenile idiopathic arthritis and severe cytokine release syndrome.[114] Its use has been studied in several trials.

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.[115] 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.[116]

It is part of the RECOVERY Trial in the UK.[9] Hoffmann–La Roche and the WHO have also launched separate trials for its use in severe cases.[117] Roche announced on July 29 that its randomized double-blind trial of tocilizumab for the treatment of pneumonia in Covid patients had shown no benefits.[118]

The REMAP‑CAP study in the UK found that tocilizumab was beneficial in adults with severe COVID‑19, who were critically ill and receiving respiratory or cardiovascular organ support in an intensive care setting, when this was started within 24 hours of the need for organ support.[114] The use of tocilizumab and its place in therapy have been updated by UK NICE in January 2021.[114]

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 and, the US) and three with no control (Italy, the US and, the US).[119]

Oral vitamin D
Oral vitamin D tablets

Many Phase II–IV clinical trials are underway to assess the use of oral vitamin D or its metabolites for prevention or treatment of COVID‑19 infection, particularly in people with vitamin D deficiency.[120][121]

A systematic review and meta-analysis of 27 publications, published in November 2020, found that vitamin D deficiency was not associated with a higher risk of having COVID-19, but found there were positive associations between vitamin D deficiency and the severity of the disease, including increases of about 80% in hospitalization and mortality rates.[122]

Other drugs
Drug Research
AnticoagulantsSeveral anticoagulants have been tested in Italy, with Low-molecular-weight heparin being widely used to treat patients, prompting the Italian Medicines Agency to publish guidelines on its use.[123] A multicenter study on 300 patients researching the use of enoxaparin sodium at prophylaxis and therapeutic dosages was announced in Italy on 14 April.[124]
APN01A 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.[125][126]
Artesunate/pyronaridineIt was announced on 3 April 2020 that pyronaridine and artesunate, the main components of a new ACT antimalarial drug sold under the brand name Pyramax,[127] showed an inhibitory effect on SARS-CoV-2 in vitro tests using Hela cells. Pyramax showed a virus titer inhibition rate of 99% or more after 24 hours, while cytotoxicity was also reduced.[128] A preprint published in July 2020 reported that pyronaridine and artesunate exhibit antiviral activity against SARS-CoV-2 and influenza viruses using human lung epithelial (Calu-3) cells.[129] It is currently in phase II clinical trial in South Korea[130][131][132] and in South Africa.[133]
AzithromycinNew York State began trials for the antibiotic azithromycin on 24 March 2020.[134]
BucillamineOn 31 July 2020, the U.S. Food and Drug Administration (FDA) authorized Revive Therapeutics to proceed with a randomized, double-blind, placebo-controlled confirmatory Phase III clinical trial protocol to evaluate the safety and efficacy of bucillamine in patients with mild-moderate COVID-19.[135]
BudesonidePatients already prescribed inhaled corticosteroids have been observed to develop less serious illness when diagnosed with COVID-19, despite often having conditions such as asthma that might be thought to lead to more serious illness.[136][137] UK-Australia trial underway as of June 2020 examining the drug as an early-intervention treatment for COVID-19, results expected in September 2020.[138]
CiclesonideJapan'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.[139]

Ciclesonide was identified as a candidate antiviral in an in vitro drug screening assay done in South Korea.[140]

CimetidineHas been suggested as a treatment for COVID-19.[141]
ColchicineResearchers 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.[142] The study, named COLCORONA, is recruiting 6000 adults 40 and older who were diagnosed with COVID‑19 and experience mild symptoms not requiring hospitalization.[142][143] Women who are pregnant or breastfeeding or who do not have an effective contraceptive method are not eligible.[143]
DipyridamoleIs proposed as a treatment for COVID‑19,[141] and a clinical trial is underway.[144]
EIDD-2801A drug developed to treat influenza. It is in Phase II trials as a treatment for COVID-19.[145][146]
FamotidineHas been suggested as a treatment for COVID-19,[141] and a clinical study is underway.[147]
FibratesFenofibrate and bezafibrate have been suggested for treatment of life-threatening symptoms of COVID-19.[141][148]
HeparinScientists have identified an ability of Heparin to bind to the spike protein of the SARS-CoV-2 virus, neutralising it, and proposed the drug as a possible antiviral.[149]
HydrocortisoneIn September 2020, a meta-analysis study published by the WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group found hydrocortisone to be effective in reducing mortality rate of critically ill COVID-19 patients when compared to other usual care or a placebo.[150]
IbuprofenA 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.[151][152]
Influenza vaccineA clinical cohort study in Brazil found that COVID-19 patients who received a recent influenza vaccine needed less intensive care support, less invasive respiratory support, and were less likely to die.[153]
Interferon betaIFN-β 1b have been shown in an open label randomised controlled trial in combination with lopinavir/ ritonavir and ribavirin to significantly reduce viral load, alleviate symptoms and reduce cytokine responses when compared to lopinavir/ ritonavir alone.<Lancet 2020;395(10238):1695-1704> IFN-β will be included in the international Solidarity Trial in combination with the HIV drugs Lopinavir and Ritonavir.[154] as well as the REMAP-CAP[155]

Finnish biotech firm Faron Pharmaceuticals continues to develop INF-beta for ARDS and is involved in worldwide initiatives against COVID‑19, including the Solidarity trial.[156] UK biotech firm Synairgen started conducting trials on IFN-β, a drug that was originally developed to treat COPD.[15]

MavrilimumabIs a human monoclonal antibody that inhibits human granulocyte macrophage colony-stimulating factor receptor (GM-CSF-R).[157][158] 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.[159]
MolnupiravirIn December 2020 scientists reported that this antiviral drug developed for the treatment of influenza can completely suppress SARS-CoV-2 transmission within 24 hours in ferrets whose COVID-19 transmission they find to closely resemble SARS-CoV-2 spread in human young-adult populations.[160][161]
nanoFenretinidenanoFenretinide is nanoparticle sized fenretinide and repurposed oncology drug approved to enter the clinic for a lymphoma indication.[162] It was identified as a candidate antiviral in an in vitro drug screening assay done in South Korea.[140] Fenretinide's clinical safety profile also makes it an ideal candidate in combination regimens.
NiclosamideIt was identified as a candidate antiviral in an in vitro drug screening assay done in South Korea.[140]
SildenafilIs proposed as a treatment for COVID-19,[141] and a Phase III clinical trial is underway.[163]

Drugs by class

Antibody

Antivirals

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.[164]

Antiparasitics

Antibiotics

Some antibiotics that have been identified as potentially re-purposable as COVID‑19 treatments:[175][176]

Immunologicals

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

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