Update: on Friday, May 1, the Food and Drug Administration (FDA) granted emergency use authorization of remdesivir as a treatment for coronavirus, citing promising test results.
The coronavirus pandemic is a serious health risk, which is why countries around the world are racing to find vaccines and treatments. Nearly 3.4 million cases of COVID-19 have been confirmed globally, and by the time you read this, the death toll will have surpassed 65,000 in the U.S. alone.
Some potential treatments listed here were previously in clinical testing for other diseases, such as cancer, allowing the trials for COVID-19 to be fast-tracked. Many aren’t aimed at the coronavirus itself but instead will hopefully reduce some of the severe side effects the disease causes, like hyperinflammation and respiratory distress.
Notably, many of the proposed treatments have gone through U.S. Food and Drug Administration (FDA) approval for other uses or are currently going through that process, meaning the route to getting approved for a clinical trial to study their effects on COVID-19 patients is shorter and faster than it would be for a new drug. Some of these are being utilized under compassionate use rules, meaning they aren’t part of clinical trials but are being administered to COVID-19 patients in life-threatening situations.
The path from trial to treatment is long and complex. As new treatments make their way to new phases, we’ll update this list. For now, we’ve excluded those in preclinical phases.
Note: These drugs are all in the early stages of testing for efficacy against COVID-19 and taking them without supervision can have tragic consequences. An Arizona man died after reportedly taking a form of chloroquine used to clean fish tanks. You’ll see a long list of potential treatments below, but many of them won’t progress to wider testing or use, because they’ll prove either unsafe or ineffective.
Antibodies
Monoclonal antibodies (mAb) are used in treatments for cancer and ebola. Made in a laboratory, these molecules work as “substitute antibodies,” according to the Mayo Clinic, boosting or mimicking the body’s immune system to attack the virus. They can do so in a variety of ways, including flagging cells for destruction and binding to different types of cells. The majority of those being researched for COVID-19 are in the pre-clinical phase, but several are in clinical trials right now.
Actemra (tocilizumab): Small proteins known as cytokines are part of the body’s immune response, released when there’s an infection. Inflammation is a side effect, as blood and other fluids flow to the source of infection. A cytokine storm is when an abundance of the proteins cause hyperinflammation, which can lead to serious complications and death. It has been reported in SARS and MERS patients and could be causing some of the more severe symptoms in some people with COVID-19. Interleukins are one group of cytokines. Actemra is a rheumatoid arthritis drug that blocks interleukin-6 (IL-6) to keep it from attacking healthy tissue when the immune system overreacts. It helped several critical COVID-19 patients recover, but a controlled clinical study needs to be performed, according to The Wall Street Journal.
Bevacizumab: In healthy adults, vascular endothelial growth factor (VEGF) promotes the formation of new blood vessels and is important for healing wounds. Some COVID-19 patients have been shown to have elevated levels of VEGF, possibly due to hypoxia (low blood oxygen) and inflammation. Bevacizumab is a VEGF blocker and has been used to treat several types of cancer for over 15 years. A clinical trial at the Qilu Hospital of Shandong University in Jinan, China will assess its effectiveness at treating shortness of breath.
Convalescent plasma: Researchers are looking at the use of blood plasma in recovered patients on those with severe symptoms from the virus. The treatment was first used in the late 1800s and has been utilized for a variety of diseases, including SARS, MERS, and the 1918 flu pandemic. The antibodies in the donated plasma are thought to help boost the patient’s immune response, but it’s still unclear how successful the treatment is. The Food and Drug Administration has listed guidelines for donators, including that they must be symptom-free for at least 14 days before giving their plasma. Erasmus Medical Center in the Netherlands, the U.K.’s National Health Service, and the University of Chicago Medicine are just a few of the institutions performing trials.
Emapalumab: Primary hemophagocytic lymphohistiocytosis (HLH) is a condition where the body’s immune cells cause inflammation by releasing too many molecules, damaging the liver, brain, and other organs. Cytokine interferon gamma (IFNγ) seems to play a role in causing the overreaction. Emapalumab is a monoclonal antibody that binds and neutralizes IFNy. Pharmaceutical company Swedish Orphan Biovitrum wants to see the drug’s effect on the cytokine storms in COVID-19 patients.
Gimsilumab: Gimsilumab is a monoclonal antibody that targets a pro-inflammatory cytokine known as a granulocyte-macrophage colony-stimulating factor (GM-CSF). Its presence can elevate the expression of pro-inflammatory cytokines, causing a kind of feedback loop that increases inflammation. GM-CSF has been found in elevated levels of COVID-19 patients admitted to the ICU, according to pharmaceutical company Roivant. It wants to test Gimsilumab as a treatment for acute respiratory distress syndrome (ARDS). The condition is caused by fluid build-up in the lungs’ air sacs and the breakdown of surfactant, so that lungs can’t fully inflate. “Targeting GM-CSF represents a promising strategy for curbing lung damage while allowing time for the virus to clear,” Dr. Elizabeth Volkmann, founder and co-director of the UCLA Connective Tissue Disease-Related Interstitial Lung Disease Program, said in Roviant’s press release.
IFX-1: The complement system helps defend against some infections, when normally inactive proteins respond to microorganisms, and the activation of one triggers a cascade of the rest. Complement component 5a (C5a) is a glycoprotein that’s part of this response, helping to mediate the inflammatory process to prevent tissue damage. Certain inflammatory diseases, including sepsis and rheumatoid arthritis, seem to result from incorrectly functioning activation of the complement system. A C5a inhibitor, like IFX-1, is designed to stop the damaging effects of inflammatory diseases. The University of Amsterdam is conducting a trial to see if it can do so in patients with severe pneumonia resulting from COVID-19.
Ilaris (canakinumab): Cryopyrin-associated periodic syndromes (CAPS) are a family of autoinflammation disorders that can cause progressive hearing loss, kidney failure, and can damage other organs. It’s the result of over production of interleukin-1-beta. IL-1ß is a cytokine that plays a role in inflammation, as well as cell proliferation and cell death. The drug ilaris is approved to treat CAPS, and researchers at a hospital in Italy, AUSL Romagna, will see if it’s useful in helping COVID-19 patients with pneumonia.
Intravenous Immunoglobulin: Intravenous Immunoglobulin (IVIG) is used to treat people with antibody deficiencies and has shown success in neurological disorders including Guillain–Barre syndrome and chronic inflammatory demyelinating polyneuropathy (CIDP). The serum is made from the blood plasma of thousands of donors, and the included antibodies are thought to help regulate the immune system, instead of specifically targeting a specific virus. Researchers are hoping IVIG can calm some patients’ overactive immune response to the coronavirus. A doctor at Sharp Memorial Hospital in California is hoping IVIG will prove effective in a clinical trial.
Kevzara (sarilumab): Like Actemra, Kevzara is a rheumatoid arthritis drug that blocks IL-6. Dr. Naimish Patel told The Wall Street Journal why blocking that cytokine could help COVID-19 patients recover: “Even though the virus is diminishing, it’s sending signals to the immune system to keep attacking.” He’s head of global development for immunology and inflammation for Sanofi, which makes Kevzara, along with Regeneron.
Lenzilumab: Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role in the growth and differentiation of blood progenitor cells. Its overexpression leads to hyperinflammation. Humanized monoclonal antibodies are made in the lab, synthesized from animals and altered to be less likely to be rejected by the human body. Lenzilumab is one such antibody, which binds to an neutralized GM-CSF. Biopharmaceutical company Humanigen, Inc. has begun a clinical trial, using the drug on pneumonia patients, assessing whether it can alleviate cytokine storms. Another pharmaceutical company, GlaxoSmithKline, is testing its own anti-GM-CSF drug, otilimab, as well.
Leronlimab (PRO 140): CCR5 is a protein on the surface of white blood cells that plays an important role in the way HIV develops in the human body. Leronlimab is a monoclonal antibody being studied as a potential treatment for HIV. It binds to the CCR5 receptor, which inhibits the release of inflammatory cytokines. Biotechnology company CytoDyn modified its clinical trial to evaluate Leronlimab’s effect on severe cases of COVID-19.
LY3127804: Angiopoietins are a family of vascular growth factors that play a role in the formation of blood vessels. Angiopoietin 2 (Ang2) is one, and it contributes to inflammatory conditions, including sepsis and acute lung injury. LY3127804 is an anti-Ang2 antibody, and pharmaceutical company Eli Lilly and Company will test its efficacy in inhibiting the angiopoietin in COVID-19 patients.
Meplazumab: Basigin (BSG) also known as cluster of differentiation 147 (CD147), is a protein and member of the immunoglobulin superfamily. It helps neighboring cells recognize one another. As a receptor, it plays an essential role in allowing the parasite that causes malaria to invade human cells. It could do something similar with the spike protein of SARS-CoV-2, the strain of the coronavirus that causes COVID-19. China’s Tang-Du Hospital will test meplazumab, an anti-CD147 antibody, on patients with pneumonia resulting from the virus.
PD-1 blocking antibody: There are two types of “tolerance” in your immune system. Central tolerance is the main way it distinguishes your own cells from outside threats, while peripheral tolerance keeps the body from over-reacting when it encounters allergens or microbes. Usually, the protein programmed cell death-1 (PD-1) helps limit T cell activity during infection to reduce inflammation. But if PD-1 binds to another protein, PD-L1, it prevents T cells from attacking cancerous cells. Monoclonal antibodies that block PD-1 are known as immune checkpoints inhibitors (ICIs). They’ve shown success in treating various types of tumors by preventing PD-1 from binding with PD-L1, freeing T cells to target the tumor. Thymosin, meanwhile, targets PD-L1. A clinical trial at Southeast University in China will study the efficacy of PD-1 and thymosin in COVID-19 patients with severe pneumonia caused by lymphocytopenia (low levels of lymphocytes, including T cells). A Clinical trial at Wuhan Jinyintan Hospital will study thymosin and camrelizumab, another PD-1 inhibitor, and another at France’s Centre Léon Bérard will study nivolumab.
Sylvant (siltuximab): Another monoclonal antibody that blocks the action of IL-6, siltuximab is approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to treat multicentric Castleman disease (MCD). This rare lymph node disease acts similarly to lymphoma, causing an overgrowth of cells. Doctors at Papa Giovanni XXIII Hospital in Italy will observe its effects on patients with COVID-19, in the hopes it will reduce inflammation in those with severe respiratory disorders.
TJM2 (TJ003234): TJM2, like Gimsilumab, is a monoclonal antibody that targets pro-inflammatory cytokine GM-CSF. In November 2019, the FDA approved it for clinical trials to treat rheumatoid arthritis. I-Mab Biopharma, which makes TJM2, is a U.S.- and China-based biopharmaceutical company. It will now explore the mAb’s effectiveness in fighting cytokine storming in patients with serious reactions to COVID-19.
Ultomiris (ravulizumab-cwvz): Paroxysmal Nocturnal Hemoglobinuria (PNH) patients lack certain proteins that protect red blood cells and the complement system mistakes them for foreign bodies and attacks them. While IFX-1 blocks C5a, eculizumab is a humanized monoclonal antibody that prohibits the C5 protein from cleaving into C5a and C5b. This can help stop them from destroying PNH patients’ red blood cells. Alexion Pharmaceuticals is testing eculizumab as a treatment for patients with severe lung injury from the coronavirus. Another drug from Alexion, ravulizumab-cwvz, is also a C5 inhibitor that’s in clinical trial for those with the same serious symptoms.
Antivirals
There are a variety of antiviral drugs for diseases like hepatitis, the flu, and herpes — many of which could potentially be repurposed to fight coronavirus. They work in different ways to stop the replication of viruses. For example, some flu antivirals are neuraminidase inhibitors. Neuraminidases are enzymes that cut acids and proteins on the surface of virus envelopes, releasing the replicated virus to infect new cells. Neuraminidase inhibitors can help reduce the amount of new viruses that are released inside the human body. The hope is that some of these antivirals will also stop the replication of COVID-19 once a patient has contracted it, lessening the duration or severity of the disease.
Arbidol (umifenovir): This broad-spectrum antiviral blocks virus entry into healthy cells by inhibiting membrane fusion. It’s not currently approved by either the EMA or FDA, though it is available in Russia and China. A study at the Guangzhou 8th People’s Hospital in China will observe its effect on patients with COVID-19. Though people are selling Arbidol on eBay in the U.K., the Medicines and Healthcare Regulatory Agency told The New Statesman, “Not only are they breaking the law, they are acting with total disregard of your health.”
ASC09: HIV requires protease enzymes to reproduce. Protease inhibitors prevent newly replicated viruses from maturing and invading healthy white blood cells. To see if the same disruption works on COVID-19, China-based biotechnology company Ascletis Pharma will test ASC09 in clinical trials.
Azvudine: (Discontinued) Azvudine is a nucleoside reverse transcriptase inhibitor (NRTI). HIV uses the enzyme reverse transcriptase in reverse transcription, converting RNA into DNA. Inhibitors block the enzyme, preventing the virus from replicating. The clinical trial for Azvudine’s efficacy against COVID-19 will take place at the People’s Hospital in Guangshan County, China.
Clevudine: Like other nucleoside analogs, clevudine mimics the naturally occurring compounds used in viral reproduction. It’s been studied as a potential treatment for hepatitis B. Researchers at Bukwang Pharmaceutical will assess how it works for COVID-19 patients.
DAS181: Influenza viruses infect cells in the respiratory tract by attaching to sialic acid (SA) on the cell’s surface. Sialidases cleave SA from the surface, so the virus cannot enter. DAS181 is an aerosolized nebulizer, so it can be inhaled as a mist to topically remove the SA from the respiratory tract cells. California biopharmaceutical company Ansun Biopharma will test DAS181 on COVID-19 patients to see if it can help prevent the proliferation of the virus in the body.
EIDD-2801: Nucleoside analogs are similar enough to naturally occurring nucleosides that they can trick RNA viruses into including building blocks during reproduction that thwart the process. They’re used in therapies for HIV, hepatitis B, and other diseases. EIDD-2801 has shown promise with MERS and SARS, and Ridgeback Biotherapeutics will start testing the drug in the U.K. to see if it has a similar effect on the coronavirus.
Favilavir/Favipiravir/T-705/Avigan: Favipiravir is a broad-spectrum antiviral that’s been utilized in Japan to treat influenza. Inside cells, it mimics the organic compound purine and eventually becomes included in the virus’s RNA strand as it grows. Exactly how Favipiravir inhibits viral RNA synthesis once it’s incorporated is unclear, but there is some indication it could be used in COVID-19 patients as well. In clinical trials in China, patients who received the medication tested negative for the virus after a median of four days; those who didn’t receive it took 11 days to test negative, according to The Guardian.
Galidesivir: Originally created as a potential treatment for hepatitis C, Galidesivir has been studied for use against a variety of viruses. It’s an adenosine analog that ends RNA elongation when it’s substituted for the naturally occurring nucleoside. BioCryst Pharmaceuticals is conducting the trial, which is funded by the National Institute of Allergy and Infectious Diseases (NIAID). The study will evaluate its safety and effectiveness in COVID-19 patients.
Ganovo (danoprevir): Ascletis Pharma developed Ganovo as a direct-acting antiviral agent (DAA) to treat hepatitis C. The efficacy of DAAs in general has been called a monumental advance over previous hepatitis C therapies. Ganovo inhibits the virus’s protease, which is necessary for its replication. The effectiveness of Ganovo, in combination with another protease inhibitor (ritonavir), will be tested at China’s Ninth Hospital of Nanchang.
Kaletra/Aluvia (lopinavir/ritonavir): Kaletra is a combination of protease inhibitors ritonavir and lopinavir, used to treat HIV. Earlier this year, The New England Journal of Medicine published the results of a study of 199 patients with severe COVID-19 patients at Jin YinTan Hospital in China. Those that received the lopinavir-ritonavir treatment saw no difference in the mortality rate. “Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit,” according to the authors of the study.
Prezcobix (darunavir): Like ASC09, Prezcobix is a protease inhibitor, used to treat HIV, in conjunction with a pharmacokinetic enhancer. Cobicistat is one such drug, which slows the breakdown of Prezcobix, allowing it to stay in the body for longer and at a higher concentration. Johnson & Johnson sent Prezcobix to Chinese health authorities in January to gauge its effectiveness in treating COVID-19. The company’s chief scientific officer, Paul Stoffels, told The Wall Street Journal that studying the drug’s effects in ill patients could help researchers find a treatment that works.
Remdesivir: This drug has gotten more press than many of the other potential treatments. It’s a broad-spectrum antiviral, and has been studied as a treatment for Middle East respiratory syndrome (MERS), a respiratory illness that is caused by the same family of viruses as COVID-19. Gilead, the company that makes Remdesivir, hoped the drug would work against Ebola, but it wasn’t nearly as effective as two other drugs at preventing death from the disease. A study published in the New England Journal of Medicine found that hospitalized COVID-19 patients that received the drug recovered around four days faster, but the researchers cautioned that “given high mortality despite the use of remdesivir, it is clear that treatment with an antiviral drug alone is not likely to be sufficient.”
Tamiflu (oseltamivir): Neuraminidase inhibitors can reduce the amount of new viruses that are released into the body by inhibiting the enzymes that cut through the virus’s envelope, allowing the replications to escape and infect more cells. That’s how tamiflu works. Though several countries stockpiled the drug several years ago in case of an influenza pandemic, it was later found to be less effective than previously thought. Due to the drug’s side effects, the WHO recommends tamiflu mainly for severely ill patients and not those who are otherwise healthy. There are a few trials for the drug’s effect on COVID-19, including at China’s Tongi Hospital and in Pakistan.
Truvada (emtricitabine and tenofovir): You may have seen commercials for this drug for what’s known as PrEP (pre-exposure prophylaxis). When taken properly, it can reduce the risk of HIV infection. Truvada is a combination of two antiretroviral medications: emtricitabine and tenofovir. Both prevent HIV from replicating, and while they work in different ways, each blocks the reverse transcriptase enzyme needed for reproduction. The Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital are conducting the clinical trial for Truvada against COVID-19.
Virazole: (ribavirin): Another nucleoside analog, viraozle works by stopping viral replication. Usually it’s used for severe pediatric respiratory infections. A recent, small trial showed it had some success in shortening the duration of COVID-19 when used in combination with other antiviral drugs. Candian-based pharmaceutical company Bausch Health Companies will further evaluate its use against the virus.
Xofluza (baloxavir marboxil): (Discontinued) Endonuclease is an enzyme that initiates flu virus replication. Polymerase acidic endonuclease inhibitors, like Xofluza, interfere with that replication. Xofluza received FDA approval in 2018 to treat the flu, and now the First Hospital Affiliated of Zhejiang University’s Medical School wants to research the drug as a treatment option for COVID-19 patients with pneumonia.
Cell therapies
Cellular therapy replaces or repairs damaged cells or tissues and is used in a range of diseases. Many types of cells have been studied for this purpose, including stem, progenitor, and primary cells. Cell therapy is being used and researched for everything from inflammatory bowel disease to cancer. CAR T-cell, for example, is a therapy in which doctors modify a patient’s T cells to identify and go after cancer cells.
CAP-1002: Cardiosphere-derived cells (CDCs) are a type of stem cell taken from heart tissue that have been shown to have regenerative properties. CDCs excrete exosomes, which carry microRNA and other material, like lipids and proteins. These sacs help with cell-to-cell communication. Researchers are studying exosomes as potential therapies for degenerative diseases. Biotech company Capricor Therapeutics, Inc. announced its CAP-1002 cell therapy will be used in compassionate care cases for COVID-19 patients with acute respiratory distress.
CYNK-001: Human natural killer (NK) cells are lymphocytes, or white blood cells, that are important to immune system function. They can recognize unhealthy cells, like tumors, and trigger cytokine release. NK therapies harness them for cancer treatments and other uses. CYNK-001, derived from human placenta, is being tested in patients with acute myeloid leukemia. Sorrento Therapeutics, Inc. and Celularity, Inc. are conducting a trial of the therapy on up to 86 COVID-19 patients.
Mesenchymal stem cells: Stem cells can self-renew through cell division and can also differentiate into different types of cells, like bone cells or liver cells. Mesenchymal stem cells (MSCs) are adult stem cells and can be taken from either humans or animals. Pneumonitis, or the inflammation of the walls in the air sacs of the lungs, is one potential side-effect of COVID-19. There has been some research on using MSCs to treat lung damage caused by radiation for cancer treatment. China’s Institute of Basic Medicine is conducting clinical trials to see the cell therapy’s effect on COVID-19 patients with pneumonitis. Celltex, Hope Biosciences, Lattice Biologics, and Mesoblast are also testing MSCs on people with the virus.
MultiStem: Biotech company Athersys created MultiStem, a stem cell product made from multipotent adult progenitor cells (MAPCs) derived from bone marrow. MPACs can self-renew and differentiate into several cell types. Acute respiratory distress syndrome (ARDS) is similar to pneumonia; it makes it difficult for the lungs to fully inflate and can lead to serious complications and death. MultiStem already underwent an early-stage clinical trial for treating ARDS, and the results showed the patients had lower mortality rates and were off ventilators more quickly than those who didn’t receive the treatment. The company is working with the FDA to fast-track a clinical trial testing for COVID-19, according to WKSU.
PLX cell product: Adherent stromal cells (ASCs) derived from human placentas are similar to mesenchymal stem cells and have anti-inflammatory and regenerative properties. Israel-based Pluristem Therapeutics has used its PLX cell product in a compassionate care case on a COVID-19 patient. For a clinical trial, researchers would explore whether the treatment can slow or prevent the overactivation of the immune response that can damage lung tissue.
Devices
In addition to drug, stem cell, and other treatments, some hospitals are using devices on critically ill COVID-19 patients. Blood purification systems removes waste products when a patient’s blood travels through a device. They’ve been used on sepsis patients to remove molecules that promote inflammation. CytoSorbents Corporation, Terumo BCT Inc., and Baxter International Inc. have all received FDA emergency use authorization for their blood purification systems. Fresenius Medical has an EUA for its continuous renal replacement therapy, which replicates kidney function by detoxifying blood. ALung Technologies has a device that removes carbon dioxide from the blood and is meant to help keep patients off ventilators. ExThera says its blood filter can actually remove the virus from blood, but it doesn’t have FDA clearance yet.
Bellerophon Therapeutics has also received an EUA for its inhaled nitric oxide (iNO) delivery system. Massachusetts General Hospital is also looking at the use of iNO on COVID-19 patients.
RNA-based therapies
RNA therapies are a fairly recent development and are being studied to treat several diseases, including macular degeneration and Zika. The therapies work in a few different ways, either by targeting nucleic acids (DNA or RNA), targeting proteins, or encoding proteins. A therapy might prevent messenger RNA from being translated into protein or it might encode a normal version of a protein instead of a mutated one. Right now, the majority of potential RNA therapies for COVID-19 are in pre-clinical phases.
OT-101: Transforming growth factor beta (TGF-β) is a cytokine that many cells secrete. It regulates embryonic development, adult stem cell differentiation, immune regulation, and inflammation. It also plays a role in the replication of viruses like Epstein–Barr. Using a blocking antibody can suppress viral transmission. Mateon’s RNA therapeutic OT-101 is a TGF-β inhibitor, and the drug developer is studying its effect on COVID-19.
Miscellaneous
There are a number of other treatments scientists are researching to see if they can help alleviate some of the severe symptoms of COVID-19. They don’t necessarily fit into the categories above.
APN01: Scientists have found that during infection, COVID-19’s viral trimeric spike protein binds to human receptor angiotensin-converting enzyme 2 (ACE2). One study showed that deactivating ACE2 caused severe lung injury in mice infected with a strain of avian influenza while administering recombinant human ACE2 was effective at lessening the damage. APN01 is a recombinant human angiotensin-converting enzyme 2 (rhACE2) created by Aperion Biologics to treat acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and pulmonary arterial hypertension (PAH). The company began a clinical trial with APN01 on COVID-19 patients in February. A similar trial is underway at the First Affiliated Hospital of Guangzhou Medical University.
ARMS-1: Cetylpyridinium chloride (CPC) is an antiseptic found in many mouthwashes and throat sprays. It’s also one of the ingredients in ARMS-I, along with other components like glycerin and xanthan gum. The spray is meant to create a barrier on mucous membranes, so viruses can’t enter, in addition to its antimicrobial properties. University Hospitals in Ohio will conduct a clinical trial with the spray on frontline healthcare providers, to see if it prevents them from contracting COVID-19 or shortens the duration of the illness if they do get it.
AT-001: A buildup of sorbitol, a sugar alcohol, is a complication of diabetes that can lead to eye and nerve damage. Researchers are looking at aldose reductase inhibitors (ARI) as a possible way to prevent that accumulation. Some severe cases of COVID-19 cause cardiomyopathy, which makes it more difficult for the heart to pump blood to the rest of the body. Biopharmaceutical company Applied Therapeutics Inc. is investigating the use of AT-001, an ARI, on critical COVID-19 patients. The company is hoping the drug can prevent damage to the heart muscles that can cause cardiomyopathy.
ATYR1923: Pulmonary sarcoidosis is a rare disease that causes lumps of inflammatory cells in the lungs. The symptoms include cough, chest pain, shortness of breath, and wheezing. It’s not clear what causes sarcoidosis, and whether bacteria, a virus, or chemicals trigger it. Biotherapeutics company aTyr Pharma, Inc. has been researching one of its treatments, ATYR1923, on this and other lung diseases. The molecule binds to neuropilin-2, which is thought to play several roles in the immune system. The company’s researchers are investigating whether ATYR1923 can reduce the overactive immune response seen in some COVID-19 patients.
Aviptadil: Vasoactive intestinal polypeptides are hormones that affect a number of tissues in the body. They dilate blood vessels and stimulate smooth muscle relaxation. Aviptadil is a synthetic form of the hormone. Its efficacy on other lung diseases, including sarcoidosis, has been studied. It’s thought to help regulate the immune response, reducing inflammation. Relief Therapeutics and NeuroRx, Inc. will test it as a potential treatment on non-acute lung injuries resulting from COVID-19.
Bemcentinib: Increased expression of the AXL gene is associated with several cancers. AXL inhibitors bind to its receptor, shutting off the pathways that the gene controls, which in turn is meant to stop tumor growth. Bemcentinib is a selective AXL kinase inhibitor that’s part of the U.K.’s Accelerating COVID-19 Research & Development platform (ACCORD) study, which fast-tracks clinical trials. As part of the study, researchers will look at bemcentinib’s effect on blocking the virus’s entry to cells via AXL.
BLD-2660: Calpains are proteins that participate in a variety of cellular functions. Some studies have shown inhibiting certain calpains suppresses viral replication of another coronavirus, SARS. A clinical trial from Blade Therapeutics is going forward for BLD2660, which is a calpain inhibitor that also normalizes levels of IL-6, an inflammatory cytokine that can cause lung damage in COVID-19 patients, the company said.
Brensocatib: Dipeptidyl peptidase 1 (DPP1) is an enzyme that functions in the maturation of neutrophils, a type of white blood cell. DPP1 activates neutrophil serine proteases, and high levels of this enzyme can damage lung tissue. Brensocatib is a DPP1 reversible inhibitor, meaning once it’s removed, the enzyme can still function. Researchers at the University of Dundee are looking into brensocatib as a DPP1 inhibitor in COVID-19 patients.
Calquence (acalabrutinib): Bruton’s tyrosine kinase (BTK) is an enzyme that’s critical to development of B cells, a type of white blood cell. Overactive signaling of B cells can lead to tumors. Calquence, from British drugmaker AstraZeneca, is a BTK inhibitor. The company’s clinical trial is based on the idea that BTK also regulates the production of some inflammatory molecules in the lungs, and inhibiting may reduce cytokine storms.
Camostat mesylate: Serine protease inhibitors are molecules involved in a variety of processes, including inflammation and blood clotting. Transmembrane protease serine 2 (TMPRSS2) is a gene that encodes a protein that’s part of the serine protease family. It’s a receptor for certain viruses to enter cells, including some influenza and coronaviruses. Camostat mesylate, a TMPRSS2 inhibitor, is part of a few clinical trials, from the University of Aarhus and Yale University, to see if it can block SARS-CoV-2 cellular entry. Nafamostat is another serine protease inhibitor that may also block the virus’s entry into cells, and it’s the subject of a clinical trial at the University of Padova in Italy. RedHill Biopharma Ltd. is partnering with the National Institute of Allergy and Infectious Diseases (NIAID) to investigate its serine protease inhibitor, RHB-107 (upamostat).
CD24Fc: In graft versus host disease (GvHD), the body’s immune system sees donated tissue or stem cells as a threat and attacks them. Proinflammatory cytokines can contribute to its development. Biopharmaceutical company OncoImmune developed CD24Fc to treat GvHD. The biologic drug binds to molecules released by damaged cells (danger-associated molecular patterns or DAMPs), preventing them from interacting with proteins called toll-like receptors. It’s meant to prevent inflammatory responses. The clinical trial will investigate whether it improves symptoms in COVID-19 patients.
Chloroquine/Hydroxychloroquine: These two antimalarial drugs have been getting a lot of attention, though their efficacy as a treatment for COVID-19 is still unknown. At least one clinical trial of chloroquine was stopped after it seemed to increase patients’ risk of heart failure, and the WHO temporarily halted its trial due to safety concerns. Malaria is caused by a parasite, while COVID-19 is caused by a virus. Malaria is caused by a parasite, while COVID-19 is caused by a virus. The reason some researchers are looking at these drugs as potential coronavirus treatments is that chloroquine and other drugs were able to block coronaviruses from infecting cells in laboratory testing. These drugs were researched as possible treatments for MERS during the 2012 outbreak. The mechanism by which these malarial drugs would work against COVID-19 is uncertain, but one hypothesis is they change cells’ surface acidity, so the virus can’t infect them. Or chloroquines might activate the immune system. “Chloroquine and hydroxychloroquine have not been appropriately evaluated in controlled studies, not to mention that they have numerous and, in some cases, very deadly side effects,” Katherine Seley-Radtke, professor of chemistry and biochemistry at the University of Maryland, wrote at The Conversation. There are a few clinical trials underway looking into their efficacy.
CM4620-IE: Calcium release-activated calcium (CRAC) channels open when levels of calcium ions get low in cells’ endoplasmic reticulum. It’s crucial for the proliferation of T cells and cytokine production. An extreme rise in calcium ion concentration has been linked to pancreatitis. Ways of inhibiting these channels have been researched as potential therapies for autoimmune or inflammatory conditions, including lung injuries. CalciMedica Inc.’s CM460-IE is a CRAC channel inhibitor that a couple of hospitals are testing as treatments for COVID-19 patients with pneumonia.
Colchicine: Gout, a type of arthritis, is caused by a buildup of uric acid. Crystals, similar to kidney stones, form in the joints, which can be painful. Colchicine is a frequently prescribed drug for gout and is thought to work by blocking the NLRP3 inflammasome, which is responsible for the production of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18. Hospitals in Canada and several U.S. states are hoping that patients with the coronavirus won’t develop cytokine storms if they administer colchicine, but the clinical trials are still underway.
Dipyridamole (Persantine): A recent study of a small number of autopsies on COVID-19 patients found that seven of 12 had undiagnosed deep vein thrombosis. Doctors are seeing patients develop blood clots, despite being on anticoagulants. It’s not clear what’s causing them. A couple hospitals in China trialed giving patients dipyridamole, an anticoagulate, but larger numbers of people would need to be tested to be more conclusive. Dociparstat sodium (DSTAT) is another anticoagulate, with antiinflammatory properties, that’s being studied in patients with acute lung injury, as is heparin.
Fadraciclib (CYC065) and seliciclib (roscovitine): Cyclin-dependent kinases (CDKs) are enzymes that participate in cell cycle regulation. CDK inhibitors are thought to curb overinflammation by encouraging the cell death of inflammatory neutrophils, a type of white blood cell. Cyclacel Pharmaceuticals, Inc. is collaborating with the University of Edinburgh to study the efficacy on two of its CDK inhibitors, fadraciclib and seliciclib, on patients with the new coronavirus.
Farxiga (dapagliflozin): Diabetes causes blood sugar, or glucose, levels to rise higher than normal. Sodium-glucose cotransporter 2 (SGLT2) transporters, found in the kidneys, are responsible for reabsorption of most filtered glucose. SGLT2 inhibitors decrease the capacity for glucose reabsorption, so it gets excreted instead, lowering the blood sugar concentration. AstraZeneca is conducting a clinical trial with dapagliflozin, its SGLT2 inhibitor, to see how it effects COVID-19 patient outcomes, for those also suffering from high blood pressure, heart disease, or chronic kidney disease.
Gilenya (fingolimod): Multiple sclerosis causes the body’s own immune system to attack nerves’ insulating layer, or myelin. The presence of pro-inflammatory white blood cells in the central nervous system can also damage the myelin sheath. A sphingosine 1-phosphate receptor modulator is believed to keep certain white blood cells (lymphocytes) from leaving the lymph nodes and crossing the blood-brain barrier, where they would further damage nerve cells. Pneumonia is an acute inflammatory response that develops in some people with COVID-19, and the First Affiliated Hospital of Fujian Medical University wants to test this MS drug’s effectiveness on reducing its severity.
Ivermectin: Ivermectin is another case where the difference between a single study and a proven, effective treatment needs to be emphasized. The drug is an anti-parasitic that’s been used to treat tropical diseases such as onchocerciasis and lymphatic filariasis, which are caused by worms. Researchers have also studied its effect on viruses. Integrase (IN) is the viral enzyme that HIV uses to insert its DNA into that of the host cell. Ivermectin inhibits importin α/β, which IN binds to in order to enter the nucleus. A recent study published in Antiviral Research found the drug inhibits the replication of SARS-CoV-2 in the lab, which is promising but not conclusive about how it will work in animals or humans. Because ivermectin is found in some pet heartworm medications, the FDA quickly issued a warning that people should not try to self-medicate. “People should never take animal drugs, as the FDA has only evaluated their safety and effectiveness in the particular animal species for which they are labeled,” the FDA wrote in its statement.
Jakafi/Jakavi (ruxolitinib): Myelofibrosis is a somewhat rare blood cancer in which fibrous scar tissue replaces spongy bone marrow. Many patients with this and a couple of other types of blood cancer have an acquired (not inherited) mutation in the Janus Kinase 2 gene. It causes bone marrow to produce too many abnormal blood cells. Janus kinase inhibitors, or JAK inhibitors, block the function of these enzymes. Because of their role in cytokine production, JAK inhibitors are also used to treat inflammatory diseases, including rheumatoid arthritis. (Cytokines are a normal part of the body’s response to infection, but an overabundance can lead to hyperinflammation.) Patients with severe reactions to COVID-19 could have an excess of cytokines causing lung inflammation. A clinical trial at Tongji Medical College of Huazhong University of Science and Technology will study the effect of Jakafi and mesenchymal stem cells on COVID-19 patients with pneumonia. Eli Lilly has also begun clinical testing of its JAK inhibitor, baricitinib.
Kineret (anakinra): The interleukin-1 receptor antagonist (IL-1RA) is a protein that inhibits the cytokine interleukin-1. Kineret is a lab-created version of this protein. It’s FDA-approved to treat rheumatoid arthritis. A recent, small study found that the drug, from pharmaceutical company Swedish Orphan Biovitrum AB, seemed to reduce the changes of COVID-19 patients exhibiting cytokine storms, but more widespread testing is needed to verify these effects.
LAU-7b (fenretinide): Retinoids are chemically related vitamin A. Fenretinide is a synthetic analogue of retinol, which is part of the vitamin A family. Researchers have studied it for the treatment of certain cancers, because it binds to retinoic acid receptors and can induce cell death, or apoptosis, in some tumors. It’s also being studied as a potential way to reduce lung inflammation in patients with cystic fibrosis. Candadian Laurent Pharmaceuticals Inc. is conducting a clinical trial to see if the drug can similarly treat over-inflammation in COVID-19 patients.
Leukine (sargramostim): While researchers are testing gimsilumab, a monoclonal antibody that targets GM-CSF, others want to give COVID-19 patients the pro-inflammatory cytokine. Sargramostim is an engineered version of granulocyte macrophage colony stimulating factor that’s been used for some types of leukemia. GM-CSF has shown resistance to influenza in mice, according to one study. Partner therapeutics will test an aerosolized version of the drug on people with acute respiratory failure, caused by the coronavirus.
Losartan: Angiotensin is a peptide hormone that constricts blood vessels and raises blood pressure. Angiotensin II receptor antagonists or blockers are prescribed for hypertension because they block the hormone. Losartan is one such drug, and the University of Minnesota is conducting clinical trials to see its effect on lung inflammation in COVID-19 patients. Radboud University is examining valsartan, and Elea Laboratories is trialing telmisartan, both other angiotensin blockers.
Metablok (LSALT peptide): Dipeptidase 1 (DPEP1) is a glycoprotein that breaks up a number of substances, including leukotrienes, inflammatory mediators produced in white blood cells. Researchers at Arch Biopartners believe DPEP1 also recruits neutrophils, a type of white blood cell, to the lungs and liver during infection, causing inflammation. Metablok is DPEP1 inhibitor, and the company is studying its efficacy on lung and kidney inflammation in COVID-19 patients.
Methylprednisolone/corticosteroids: Methylprednisolone is a synthetic corticosteroid, which mimics how the body’s hormones work to reduce inflammation. Corticosteroids are used to treat a plethora of conditions, from asthma to lupus to arthritis. Though they were used during severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) outbreaks, the World Health Organization doesn’t currently advise the use of corticosteroids for COVID-19, according to a February article from The Lancet. Clinical trials for glucocorticoid therapy are going forward at Peking Union Medical College Hospital and Tongji Hospital.
MN-166 (ibudilast): Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine, and its overexpression is associated with several types of cancer. Ibudilast is an MIF inhibitor that’s approved in Japan and Korea to treat asthma. Yale researchers are studying its effect on COVID-19 patients with acute respiratory distress syndrome.
MRx-4DP0004: A live biotherapeutic product (LBP) contains live organisms, like bacteria, and is used for prevention or treatment of a disease. MRx-4DP0004 is a strain of bifidobacterium breve, a microbe found in the gastrointestinal tract. It’s been studied as a way to reduce proinflammatory cytokines in asthma. 4D Pharma, which makes the product, wants to see if it has similar effects on hyperinflammation caused by the new coronavirus.
Nitazoxanide: Nitazoxanide is a drug that’s used for diseases caused by parasites, like cryptosporidiosis and giardiasis. Previously, researchers studied it as a possible treatment for MERS, because it inhibits the nucleocapsid (N) protein and interferes with replication of the virus. The drug is involved in a couple of clinical trials for COVID-19, including one at Tanta University in Egypt.
Novaferon: Interferons are cytokine mediators that alert the immune system when there’s a viral infection. Lab-made interferons are used to treat several diseases, including hepatitis B. Exactly how interferons affect the virus is unclear, but it’s thought to interfere with its life cycle, while also boosting cell-mediated immunity. Novaferon is one man-made interferon used to treat hepatitis B, and the First Affiliated Hospital of Zhejiang University Medical School will study whether it’s effective against COVID-19. Researchers are also studying other interferions as potential COVID-19 treatments. BetterLife Pharma Inc. recently announced a study involving interferon alpha-2b, and Eiger wants to evaluate if peginterferon lambda shortens the duration of the virus in a clinical trial.. (A pegylated or peginterferon has been modified with polyethylene glycol to help cloak it from the body’s immune system.)
Opaganib (yeliva): Sphingosine kinases are lipid enzymes that catalyze the conversion of the sphingosine to sphingosine-1-phosphate (S1P), and this pathway has been linked to some cancers and inflammatory diseases. RedHill Biopharma, the maker of opaganib thinks the an oral sphingosine kinase-2 selective inhibitor may also reduce levels of IL-6 and tumor necrosis factor (TNF), two cytokines that mediate inflammation. The company is examining its impact in moderate-to-severe COVID-19 infections.
Pacritinib: Pacitinib is another drug in clinical trials for the treatment of the blood cancer myelofibrosis, which can be caused by an acquired mutation in the Janus Kinase 2 gene. If the JAK2 protein is continuously activated, it can lead to an overproduction of abnormal blood cells. Pacitinib is a JAK2 inhibitor that blocks the function of certain kinase enzymes, including interleukin-1 receptor-associated kinases (IRAK1), which are thought to be involved in some inflammatory diseases. The drug is also a colony-stimulating factor 1 receptor (CSF1R) inhibitor and may reduce an overabundance of white blood cells. CTI BioPharma Corp. will conduct a clinical trial on COVID-19 patients, including some with cancer.
Pepcid (famotidine): Amid the 2003 SARS outbreak, researchers looked for effective ways of inhibiting coronaviral proteases, or enzymes that break down proteins. Papain-like protease (PLpro) is necessary for coronavirus replication but also helps it hide from the infected person’s immune system by removing certain proteins from cell surfaces. Infectious diseases specialist Dr. Michael Callahan noticed some elderly COVID-19 patients who survived in Wuhan, China were on famotidine (or pepcid), a common heartburn medicine. It’s possibly working as PLpro inhibitor. There’s currently a clinical trial underway in New York, with doctors giving patients very high doses of the drug. It’s too early to tell how effective the drug is, but people started “hoarding” the medication after news of the trial appeared in Science. It’s currently in short supply, according to the FDA. Doctors are cautioning people about taking the medication because of the study, according to CNN.
Piclidenoson: Depending on the associated disease and where it was found, the A3 type of receptor for the nucleoside adenosine can either promote or reduce inflammation. Can-Fite BioPharma Ltd. said its drug piclidenoson, an A3 adenosine receptor agonist, can induce an anti-inflammatory effect, and it’s undergoing a clinical trial on COVID-19 patients with moderate-to-severe symptoms.
PUL-042: Toll-like receptors (TLRs) detect microbial infection and martial the appropriate immune response. PUL-042 is an inhaled solution made up of two TLR binders. Once inhaled, they bind to and activate the TLRs in lung epithelial cells, which then produce a variety of molecules and free radicals to protect against the virus, bacteria, or other invader. The other TLR binder activates the production of several types of white blood cells. Together, it’s meant to prevent an infection’s progression. The clinical trial for the drug, made by Pulmotect, Inc., will see if it’s effective on patients in early stages of COVID-19 infection.
Rebif (interferon beta-1a): Interferon beta-1a is an interferon used to treat multiple sclerosis. Exactly how Rebif, an interferon made by Merck KGaA, works in MS patients isn’t known, but it does lessen inflammation and reduce the body’s immune response that damages the myelin sheath. The French Institut National de la Santé et de la Recherche Médicale (INSERM) will use Rebif in a clinical trial, to see if it similarly reduces inflammation in COVID-19 patients. In the U.K., pharmaceutical company Synairgen is testing an inhaled version of its interferon beta-1a treatment, SNG001. It’s possible the virus is suppressing the body’s production of the interferon, and the inhaled dose could stimulate the immune response, an executive at the company told the BBC.
Selinexor: A nuclear envelope is the membrane separating the nucleus from the cytoplasm in eukaryotic cells. Macromolecules — like carbohydrates, lipids, and proteins — pass back and forth with the help of transport proteins. Usually, the export of certain proteins by a transport protein known as exportin-1 (XPO1) inhibits the growth of tumors, but in cancer cells it actually promotes their formation. A selective inhibitor of nuclear export (SINE) compound, selinexor works by binding to exportin-1, so the proteins can no longer pass between the nucleus and cytoplasm, leading to the cell’s death. XPO1 may also be involved in COVID-19 inflammatory response, as well as its replication. To test the efficacy of selinexor on the virus, Karyopharm Therapeutics Inc. is conducting a clinical trial.
Solnatide: Tumor necrosis factor (TNF), an inflammatory cytokine, works to defend the human body against invading pathogens. It participates in the regulation of fluid in the alveoli, or air sacs, in the lungs. A synthetic peptide, solnatide, mimics what’s called the lectin-like domain (TIP) of TNF, stimulating reabsorption of the fluid, decreasing inflammation. Solnatide is a potential treatment for pulmonary edema (a buildup of fluid in the lungs), and pharmaceutical company Apeptico will study an aerosolized version of the drug, to see if it helps COVID-19 patients with acute respiratory distress syndrome (ARDS).
Tissue plasminogen activator (tPA): Plasminogen is a protein found in the blood that gets converted to plasmin, an enzyme. Plasmin breaks down clots. A tissue plasminogen activator (tPA) spurs the catalyst of plasminogen to plasmin. Because doctors are finding evidence of clots in a number of COVID-19 patients’ lungs, kidneys, and blood vessels, researchers at MIT and the University of Colorado at Denver are helping several hospitals test the treatment on patients with COVID-19.
Tradipitant: Neuropeptides, including tachykinin, are small molecules neurons use to communicate with one another. Neurokinin-1 is a tachykinin receptor. Substance P is a mediator of pain transmission and binds to that receptor. It also binds to other types of cells, including white blood cells. Neurogenic inflammation occurs from the release of substance P and other mediators; it’s linked to several conditions, including eczema. Tradipitant is a neurokinin-1 receptor antagonist, meaning it blocks the receptor so it can’t interact with substance P. Vanda Pharmaceuticals will study tradipitant’s ability to reduce inflammation in COVID-19 patients.
Vazegepant: Calcitonin gene-related peptide (CGRP) is a peptide, or amino acid chain, produced in both central and peripheral neurons (that is, those found in the brain and spinal cord, as well as the nerves elsewhere in the body). It’s been found that CGRP levels increase during migraines, and the peptide dilates blood vessels in the brain and amplifies pain signal transmission. Researchers at Biohaven Pharmaceutical believe the release of CGRP participates in symptoms of COVID-19, like cough and fever, as well as the increase of IL-6, a cytokine. Vazegepant is the company’s CGRP receptor antagonist or blocker, and the clinical trial will test its ability to lessen lung inflammation in patients receiving supplemental oxygen.
Washed microbiota transplantation: (Discontinued) Some people who take antibiotics end up wiping out their colon of the healthy bacteria that help stave off clostridium difficile (C. difficile), which can lead to a serious infection. Fecal microbiota transplantation (FMT) reintroduces healthy bacteria via a donor’s stool, transferred by colonoscopy or another procedure. The washed microbiota process is a way of purifying the sample beforehand. A clinical trial at the Second Affiliated Hospital of Nanjing Medical University is doing a clinical trial on the procedure to examine its effect on COVID-19 patients with antibiotic-associated diarrhea.
Correction: An earlier version of this article misstated the drug being studied by the Qilu Hospital of Shandong University. Researchers there are studying Chinese bevacizumab, a generic drug similar to Avastin.
