15 drugs that may cure coronavirus
April 15, 2020 10:04 AM
Scientists worldwide are working on finding the cure against the novel coronavirus. So far, there are two major approaches: test the currently available on the market drugs and supplements and see if any will fight off the virus and create the new vaccine.
Researches focus on two approaches to the treatment of the novel coronavirus. The first one is using the drugs, supplements and treatment methods currently available on the market that happen to provide antiviral effects. Another one is creating the vaccine, which may take a long time and money to happen.
Let’s see what drugs are currently considered or developed by researchers.
Chloroquine and less toxic hydroxychloroquine are used for the prevention and treatment of malaria. Due to their ability to reduce immune activity, these drugs are also used to treat autoimmune disorders, such as rheumatoid arthritis and lupus. In March 2020 the FDA issued an Emergency Use Authorisation that allows patients with COVID-19 to be treated using drugs with no clear evidence of their efficacy, approving limited emergency use for both drugs as a treatment for COVID-19. The medicines have quickly gotten into the media spotlight and were mentioned even by the President of the United States, Donald Trump. However, the European drugs regulator has claimed that while studies on both drugs are ongoing in COVID-19, they must not be used outside authorised uses. The use in clinical trials or nationally agreed protocols is allowed.
Indeed, Chloroquine has shown some antiviral effects. It is able to change the pH of the parts in which viruses get into the cell, hindering the virus’ ability to reproduce. A 2020 study by Chinese scientists with cultured cells infected by SARS-CoV-2 has shown that chloroquine administration may keep the virus from spreading.
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The International Journal of Antimicrobial Agents Meanwhile has published the results of a small-scale study evaluating the effectiveness of antimalarial drugs, such as Chloroquine and hydroxychloroquine against COVID-19. The combination of hydroxychloroquine and an antibiotic called azithromycin helped to reduce both the duration and symptoms of COVID-19.
Even though Chloroquine has been used for a long time as an antimalarial drug, it may cause severe side effects, including death, if taken incorrectly. Even if taken as intended, the medication can cause stomach distress or permanent damage to a vision. Healthcare providers are warned that the optimal dosing of the drug and duration of treatment for COVID-19 are unknown and instructed to control heart activity concerning potential drugs’ side effects.
The promising results of studies with Chloroquine are considered the very first step that should lead to more complex clinical studies and competing peer studies to prove its effectiveness. Multiple clinical trials by government agencies and academic institutions are ongoing. Study results published in the International Journal of Antimicrobial Agents has found that the combination of hydroxychloroquine and antibiotic azithromycin (brand names Zithromax or Azithrocin) might be effective in treating the COVID-19 coronavirus and shortening the duration of the virus in patients.
Remdesivir is an antiviral drug developed by Gilead Sciences. Remdesivir is an analogue of adenosine; therefore, it can incorporate into emerging viral RNA chains and cause their premature termination. Remdesivir was used as a treatment for Ebola virus disease, Marburg virus infections, and single-stranded RNA viruses, including coronaviruses (including MERS and SARS viruses).
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Remdesivir can interfere with the RNA, needed for virus replication. In the body, it is metabolised into a nucleotide analogue that is similar to adenosine, the RNA essential building block. It weakens the ability of the virus to produce its new RNA copies by suppressing an enzyme called RNA-dependent RNA polymerase. That is especially effective against viruses that only use RNA as their genetic material, without the DNA stage. A 2020 study with the use of a clinical isolate of 2019-nCoV in vitro, has shown that Remdesivir might inhibit virus infection efficiently in a human cell line. Therefore, Remdesivir can act as a broad-spectrum antiviral, which is useful for diseases caused by RNA viruses such as cold, influenza, and Covid-19.
Gilead Sciences has announced clinical trials with plans to enrol up to 1000 patients and has also made the drug available for compassionate use in emergency cases. The European Union’s health regulator has not approved Remdesivir for COVID-19 but recommended it for compassionate use, including its use for clinical trials.
Favilavir (Avigan, Favipiravir)
Favilavir is an antiviral drug developed by Toyama Chemical, Fujifilm group of Japan, that has activity against RNA viruses. In animal studies, it has shown an effect against influenza viruses, yellow fever virus, West Nile virus, foot-and-mouth disease virus.
Favilavir can selectively inhibit viral RNA-dependent RNA polymerase, an enzyme that activates the replication of RNA from an RNA template. It may also generate lethal RNA transversion mutations, creating a nonviable viral phenotype. In practical terms, it means that drugs may prevent patients with low or moderate viral load from becoming sicker.
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In February 2020 regulatory officials in China approved Favilavir as an investigational therapy for the use as a treatment for the COVID-19. The approval was based on the efficacy of the medicine against the infectious disease in clinical tests with 70 patients conducted in Shenzhen, Guangdong province. However, some minor effects had also been recorded. At present, the generic version of Faviliavir was being mass-produced in China and promoted with the label Avigan. However, further work on pharmacy and clinical pharmacology research is required. Despite the positive results of the clinical trials and mass production of the Favilavir, it should be approved by the FDA to be considered as an effective treatment medicine for coronavirus. Japan’s government is also waiting on the results of their own clinical trials before producing the drug on a mass scale domestically.
Lopinavir/ritonavir (LPV/r), known under the brand name Kaletra and others, is a medication for the treatment and prevention of HIV/AIDS. The drug was created by Abbott Laboratories (now Abbvie). It is generally used with other antiretroviral drugs to treat HIV-1 infection in adults and pediatric patients 14 days and older. Ritonavir enhances the effect of lopinavir, and the combination of two drugs significantly reduces the morbidity and mortality in patients with HIV / AIDS. LPV/r has been approved by the US Food and Drug Administration and in Europe.
A 2004 study has shown that LPV/r might be a promising treatment option for COVID-19. In essence, patients treated with these drugs in combination with ribavirin had a decreasing viral load and rising peripheral lymphocyte count. Countries heavily affected by COVID-19, such as Italy, were recommended the drug combination for the novel coronavirus treatment.
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There are numerous ongoing trials, evaluating the lopinavir-ritonavir effect on COVID-19. Two trials examined how the drug’s combination could act against pneumonia induced by COVID-19. An ongoing randomised controlled trial from Tongji Hospital of lopinavir-ritonavir is testing abidol hydrochloride, oseltamivir and lopinavir/ritonavir in the treatment of viral pneumonia. Another study conducted in South Korea is investigating whether hydroxychloroquine or lopinavir/ritonavir can reduce the viral load from a respiratory specimen in COVID-19 patients with mild symptoms. The World Health Organization is conducting a multi-centre, adaptive, randomised, open clinical trial to assess the safety and efficacy of hydroxychloroquine, remdesivir and standard of care in adult patients with COVID-19. However, a clinical trial published in the New England Journal of Medicine has shown that treatment with lopinavir-ritonavir brought no difference from standard care in the time to clinical improvement in patients with cases of severe COVID-19. Therefore, the current clinical trial in South Korea and the Tongji Hospital are expected to prove or refute the effectiveness of LPV/r against COVID-19.
The most common adverse effects of lopinavir/ritonavir are diarrhoea and nausea. Other common adverse effects include asthenia, abdominal pain, headache, vomiting, and rash. People with structural heart diseases, preexisting conduction system abnormalities, cardiomyopathies or ischaemic heart disease should use these drugs with caution.
Tocilizumab is an immunosuppressive drug, developed by Hoffmann–La Roche and Chugai and mostly used for the treatment of systemic juvenile idiopathic arthritis and rheumatoid arthritis. It is sold under the trade names Actemra and RoActemra.
A 2020 research from China has shown that Tocilizumab may be an effective treatment for patients diagnosed as severe or critical COVID-19. Within a few days, the treatment caused positive results: temperature and oxygen intake lowering, lung lesion opacity absorption, normalisation of lymphocytes and C-reactive protein level. No significant reactions were observed.
Genentech from the Roche Group and the US Biomedical Advanced Research and Development Authority have launched a randomised, controlled trial (COVACTA) to evaluate the safety and efficacy of intravenous Actemra (Tocilizumab) and care standards in adult patients with severe COVID-19 pneumonia.
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Actemra (Tocilizumab) has been approved in China for the treatment of patients with the COVID-19, who have also developed severe lung damage and have high levels of IL-6 in the blood. The studies have suggested that an elevated level of IL-6, a biomarker for inflammation and high-level immune response, may be lethal for people with community-acquired pneumonia.
The mechanism of Tocilizumab includes an interruption of the process of ‘cytokine release syndrome’ (CRS), a complication in the form of severe inflammatory response.
However, Actemra is not currently approved for this use by the FDA. The most frequent adverse effects observed in clinical trials are upper respiratory tract infections, common cold, headache, high blood pressure and total cholesterol levels.
REGN3048–3051 and Kevzara
REGN3048–3051 is the combination of neutralising monoclonal antibodies REGN3048 and REGN3051 developed by Regeneron Pharmaceuticals Inc. First-in-human clinical trial supported by the National Institute of Allergy and Infectious Diseases (NIAID) researches if it may act effectively against coronavirus infection. The tolerability and safety of this drug will be tested in 48 patients. The antibodies of the drug can bind to S-protein of MERS coronavirus. The studies on mice in the case of MERS lead to the potent neutralisation of the MERS in blood and lowered viral loads in the lungs.
Pharmaceutical companies Regeneron Pharmaceuticals Inc. and Sanofi SA have also announced plans to launch clinical trials on their arthritis drug Sarilumab (trade name Kevzara) in patients with severe COVID-19 infection. It can inhibit interleukin-6 (IL-6), which causes an overactive inflammatory response in the lungs of infected patients.
EIDD-2801 is a broad-spectrum oral antiviral. It can interfere with the virus to replicate once it infects a cell, which makes it similar to remdesivir, a drug currently being studied in COVID-19 patients. Both drugs can mimic ribonucleosides — the components of RNA molecules — causing errors when the drugs get into viral RNA during replication and preventing the virus spread. Researchers have shown that EIDD-2801 may be used as either a prophylactic or a therapeutic medicine for SARS-CoV-2. The drug has also shown efficacy against other coronaviruses, such as SARS-CoV and MERS-CoV.
EIDD-2801 has one advantage over Remdesivir: it can be used as a pill, while Remdesivir must be given intravenously. It means that it can be administered outside of a clinical setting for prophylaxis.
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EIDD-2801 was first tested in cells cultured in the laboratory. When those tests appeared to be encouraging, the scientists gave the drug to mice infected with coronaviruses. A paper describing the study results was published in the journal Science Translational Medicine. When EIDD-2801 was used as a prophylactic, it could prevent severe lung damage, reduce the viral load and weight loss in infected mice if given from 12 to 48 hours after the infection began.
Here is an exciting aspect of the drug: viruses that can carry Remdesivir resistance mutations happen to be more susceptible to EIDD-1931 and vice versa. It means that both drugs may be combined to improve efficacy and prevent resistance.
Clinical studies of the drug in humans were expected to begin in spring 2020. If EIDD-2801 proves to be effective, it may be used not only for the COVID-19 pandemic but also in managing other coronavirus outbreaks in future.
Anakinra is a biopharmaceutical drug for the treatment of rheumatoid arthritis. It is a recombinant and modified type of the human interleukin 1 receptor antagonist protein, marketed by Swedish Orphan Biovitrum.
Studies have shown that patients with severe COVID-19 may have cytokine storm syndrome, an excessive immune response. Usually, COVID-19 is treated with supportive measures. The most often cause of mortality and respiratory failure is acute respiratory distress syndrome (ARDS). The disorder named sHLH comprises hyperinflammatory syndromes and is defined by a “cytokine storm” with multiorgan failure. This process increases the number of proinflammatory cytokines such as IL-1, IL-6, IL-12, and IL-18, as well as interferon gamma and tumour necrosis factor. The disease is characterised by continuous high fever, hepatosplenomegaly, central nervous system manifestations, and thrombocytopenia.
In adults, sHLH is generally caused by viral infections. Pulmonary involvement, such as ARDS, occurs in approximately half of all patients.
Studies have shown that Anakinra may calm the cytokine storm, meaning its administration may be useful for patients with COVID-19. The most common side effects following Anakinra use include injection site reactions, headaches, and higher levels of cholesterol in the blood.
Galidesivir, also known as BCX4430 and Immucillin-A, is an antiviral drug, an analogue of adenosine. The drug was developed by BioCryst Pharmaceuticals to treat hepatitis C but then developed as a potential treatment for Ebola and Marburg virus diseases, and Yellow fever. Galidesivir shows broad-spectrum antiviral effect against RNA viruses, such as bunyaviruses, paramyxoviruses, arenaviruses, flaviviruses, coronaviruses, and phleboviruses. It acts as a nucleoside RNA polymerase inhibitor and disrupts the viral replication.
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So far, Galidesivir is being evaluated for yellow fever in a Phase II trial according to the contracts with the National Institute of Allergy and Infectious Diseases (NIAID) and the US Department of Health and Human Services (HHS).
SNG001 includes naturally occurring IFN-β, administered through a nebuliser. It was initially produced to prevent severe lower respiratory tract infections in the lungs that were caused by cold and flu to reduce the severity of the infection caused by the coronavirus.
The human body can produce its own interferon-beta to alleviate inflammation caused by the body’s immune response. Scientific research shows that IFN-β deficiency in the lungs might explain the high susceptibility of vulnerable patient groups who have developed severe lung disease during viral infections. SNG001 may provide IFN-β directly to the lungs, replenishing the deficiency.
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Clinical trials led by the scientists at the University Hospital Southampton in patients with asthma have shown that treatment with inhaled SNG001 lowered viral lung pathology and lung load in an in vivo swine flu driven model of viral pneumonia. The pilot phase has shown positive results. The drug has been well-tolerated in clinical trials in more than 200 respiratory patients. Phase II of clinical trials in patients with asthma have shown that SNG001 is well-tolerated, might enhance the lungs’ antiviral ability and improve lung function during cold or flu infection.
TAK-888 is anti-SARS-CoV-2 polyclonal hyperimmune globulin (H-IG) produced by Japanese pharmaceutical giant Takeda. In March 2020, Takeda announced the development of TAK-888 for the treatment of high-risk individuals. To develop the treatment, scientists will need to get plasma from people successfully recovered from the COVID-19.
Plasma derived-therapies, including hyperimmune globulins, have earlier been shown to be effective in the treatment of severe acute viral respiratory infections and are considered as a potential treatment for COVID-19
The blood-derived antibodies from recovered patients are found to improve the immune system responses in infected patients. The novel treatment has shown promising preliminary results in activating the immune system against the disease. The plasma with antibodies is planned to be administered into critically ill patients. Takeda intends to make the plasma product available for COVID-19 patients in 9–18 months.
Ivermectin is a medication used for the treatment of parasite infestations, such as head lice, scabies, river blindness, trichuriasis, lymphatic filariasis, and ascariasis. The drug works by increasing the parasite’s cell membrane, resulting in their paralysis and death. Ivermectin is FDA-approved for a number of parasitic infections and has an established safety profile for human use. Usual side effects of the drug include red eyes, dry and burning skin. It is not clear if Ivermectin is safe for pregnant women, but maybe probably acceptable during breastfeeding.
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Ivermectin has been shown to stop many viruses, such as HIV, dengue, Zika and influenza, from replicating, at least in the laboratory. The latest laboratory data from Monash University and the Doherty Institute suggests that Ivermectin is able to stop SARS-CoV-2 from replicating in up to 48 hours. Their report shows that Ivermectin is worthy of further consideration as a potential SARS-CoV-2 antiviral.
Ivermectin is thought to stop the processes that allow proteins to move within the virus. These proteins enable the virus to replicate and enhance the infection.
To evaluate possible benefits of the drug in COVID-19 patients, the scientists plan to examine a dosing regimen as, during the clinical trial, a single daily dose was found to be safe but no clinically benefit.
AmnioBoost is a natural amniotic fluid supplement by Lattice Biologics. The fluid is taken from healthy, non-related, living donors during a Caesarian delivery. AmnioBoost contains useful proteins, growth factors and signalling molecules that support a healthy tissue environment and help to restore balance to the synovial milieu and cushions. Due to its benefits, AmnioBoost is used for the treatment of joint pain and chronic adult inflammatory conditions such as osteoarthritis.
Lattice Biologics is exploring the efficacy of AmnioBoost in the treatment of acute respiratory distress syndrome (ARDS), which is one of the most common causes of death in COVID-19 infection and is associated with older age, co-morbidities such as diabetes, disease and inflammation severity. AmnioBoost has shown efficacy in alleviating the inflammatory conditions caused by several diseases, including coronavirus. The drug is thought to reduce the production of proinflammatory cytokines while boosting the production of anti-inflammatory cytokines and facilitating staffing tissues with naturally occurring anti-inflammatory cells. That helps to fight off the inflammatory processes caused by several diseases. Such an opinion is supported by the clinical study conducted in China, suggesting that allogeneic mesenchymal stem cells (MSCs) might treat or significantly improve functional outcomes in patients with severe COVID-19 pneumonia.
Several pharmaceutical companies have begun working on antibody treatment for the patients infected with COVID-19. The Indianapolis drugmaker Eli Lilly is working with AbCellera to start testing an antibody therapy designed for the treatment and prevention of COVID-19 in humans. AbCellera identified more than 500 human antibodies that could be potent against the virus from a blood sample of a recovered coronavirus patient.
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AbCellera received a blood sample from a US patient recovered from COVID-19, then screened more than 5 million immune cells searching for those that could make functional antibodies. As a result, the company has identified more than 500 unique fully human antibody sequences that might help patients to neutralise the virus and recover from the disease. The next step was to find the most antibodies effective in neutralising the novel virus. Most of these antibodies will be identified in cooperation with the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases. They will be tested for their ability to neutralise the virus.
Vir Biotechnology, Inc. has announced a collaboration with the National Institutes of Health and the National Institute of Allergy and Infectious Diseases, Vaccine Research Center to research and develop human monoclonal antibodies against coronaviruses, such as SARS-CoV-2. Vir Biotechnology, Inc. has identified numerous monoclonal antibodies that can bind to SARS-CoV-2. These antibodies were taken from people who had recovered from a SARS infection. The current research aims to define if these antibodies may be an effective treatment or prophylaxis against SARS-CoV-2.
This treatment involves taking blood plasma from people who have recovered from the COVID-19. Their plasma contains antibodies that could fight against the virus and improve immune response.
The trials published in the Journal of the American Medical Association and the journal PNAS have shown promising results on patients critically ill with COVID-19.
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The first trial researched if the administration of convalescent plasma transfusion might be useful in the treatment of severely ill patients with coronavirus disease. In this trial, five critically ill patients with COVID-19 and acute respiratory distress syndrome (ARDS) were administered convalescent plasma with high virus-specific IgG and IgM ELISA titers. The trial resulted in viral load decline and the improvement of clinical conditions of these patients as well as the body temperature reduction, improved chest imaging and Pao2/Fio2. It increased neutralising antibody titers, which is important for the restriction of viral infection. Four patients who were on mechanical ventilation and ECMO no longer needed respiratory support in 9 days after plasma transfusion. The results of the study have shown that antibodies from convalescent plasma may benefit the clearance of the virus and improve the symptoms of the disease.