Treatments
COVID-19 drug development
https://en.m.wikipedia.org/wiki/COVID-19_drug_development
Remdesivir
"There is only one drug right now that we think may have real efficacy and that's remdesivir," WHO Assistant Director-General Bruce Aylward said at a March press briefing.
One of the most promising antiviral drugs for Ebola got quick NIH approval for testing on COVID-19 patients.
The drug remdesivir is being studied in people with COVID-19. It works by stopping the coronavirus from making copies of itself. The FDA is now allowing remdesivir to be used in adults and children hospitalized with COVID-19 disease, as it may shorten the recovery time in some people. Side effects of remdesivir can include abnormal liver tests and reactions when the drug is given, such as low blood pressure, sweating and chills. Studies are still going on to learn more about how safe and effective remdesivir is in treating COVID-19.
Gilead Sciences Initiates Two Phase 3 Studies ofInvestigational Antiviral Remdesivir for the Treatment of COVID-19
-- U.S. FDA Grants Investigational New Drug Authorization to Study Remdesivir for the Treatment of COVID-19 --
https://en.m.wikipedia.org/wiki/Remdesivir
Remdesivir, a broad-spectrum antiviral, is viewed by researchers and doctors as one of the most promising agents against Covid-19 to enter human trials to date. In lab studies conducted prior to the Covid-19 outbreak on numerous compounds, researchers at the University of North Carolina and Vanderbilt University found the drug had potent activity against against a wide variety of coronaviruses similar to the new coronavirus
Two-Thirds of Severe Covid-19 Cases Improved on Gilead Drug. All received remdesivir for up to 10 days on a compassionate use basis, a program that allows people to use unapproved medicines when no other treatment options are available. Over 18 days, 68% of the patients improved, with 17 of the 30 patients on mechanical ventilation being able to get off the breathing device. Almost half of the patients studied were ultimately discharged, while 13% died. Mortality was highest among those who were on a ventilator, with 18% of them dying.
Several large scale clinical trials are underway to evaluate the benefit of remdesivir for Covid-19, the disease caused by the novel coronavirus that has infected more than 1.65 million people worldwide and killed 100,000. One that was conducted in China could report results this month. Another, sponsored by the U.S. National Institutes of Health, has enrolled patients rapidly as the virus spread throughout the U.S. It could also report results in the coming weeks. Gilead itself is sponsoring an additional two trials.
If it works well, one issue will be whether there is enough of a supply of the drug, especially if the epidemic is still raging. Gilead has been working all-out to bolster supply of the hard-to-make medicine. It said earlier this month that it hopes to to have 500,000 treatment courses by October, and more than 1 million by year-end. Production time has also been accelerated to six months from one year
Gilead Has Treated More Than 1,700 COVID-19 Patients With Remdesivir
Two-Thirds of Severe Covid-19 Cases Improved on Gilead Drug
Trials of Gilead Coronavirus Drug in China Could Start Next Week
Chinese company makes copy of patented coronavirus treatment remdesivir
Gilead aims to produce one million remdesivir treatment courses
Ramping up remdesivir supply, Gilead gifts 1.5 million doses for COVID-19
COVID-19 update: Gilead ramping up remdesivir production; Codagenix partners with vaccine giant
JUN 26, 2020 - Gilead on Monday said it aims to manufacture another 2 million courses of remdesivir this year, but did not comment on how it plans to distribute, or sell, those supplies for use by hospitals. The company has licensed the antiviral to several generic drugmakers, who will be allowed to sell the medication in over 100 low-income nations.
Gilead Science Releases Pricing Plan For COVID-19 Drug Remdesivir
U.S. government $390 a dose, which will cost patients on Medicare at least $2,300 for the shortest coronavirus treatment cycle.
Hospitals $520 per dose, in turn, costing patients with private insurance at least $3,100 per treatment cycle.
Special Report: As doctors see hope in new treatments
Plaquenil & Aralen (Antimalarial Drugs chloroquine and hydroxychloroquine)
For centuries people have turned to hydroxychloroquine and chloroquine to fight malaria. Now these drugs, often sold under the brand names Plaquenil and Aralen, are being sent to clinical trial for fighting COVID-19. These drugs had been used during the SARS crisis and showed promise, but were never widely used. They may be useful for both preventing infection and treating people with infections. Chloroquine has been shown to inhibit the growth of the novel coronavirus in lab settings, and has been used in China to treat critically ill patients.
However, people should not take this medication without a doctor’s supervision. In Nigeria, three people were reported to have overdosed on chloroquine after the U.S. president made positive comments about it in relation to COVID-19. Publicity of these drugs long before the president’s comments had already led to a nationwide shortage of these drugs in the U.S. Pharmacists began running out of their supply of a drug that can be lifesaving in the event of lupus flares. Many people with rheumatoid arthritis also rely on hydroxychloroquine for their flares.
The label for Plaquenil, a brand of hydroxychloroquine, is an anti malaria drug that has been around since 1955.
Novartis, Mylan and Teva to supply tens of millions of chloroquine tablets to fight COVID-19
- Novartis will donate enough doses of malaria drug hydroxychloroquine to treat several million patients in the fight against the coronavirus, if it wins approval, the Swiss company said on Friday.
- There are no vaccines or treatments approved for the disease, but there is currently a 1,500-person trial, led by the University of Minnesota, to see whether hydroxychloroquine can prevent or reduce the severity of COVID-19.
- Novartis makes the malaria drug, which is also used to treat lupus and rheumatoid arthritis, at its Sandoz unit in the United States.
- https://www.google.com/amp/s/www.cnbc.com/amp/2020/03/20/novartis-to-donate-malaria-drug-in-fight-against-coronavirus.html
By March 18, the day before Trump first uttered the word "hydroxychloroquine" in public, Boulware had already recruited 61 study subjects, according to his research website.
In days, Boulware accomplished what he says usually takes more than a year to do.
"For clinical trials, this has by far been the fastest of my career," he said. "I think it's broken world records."
The other seven centers conducting hydroxychloroquine studies for coronavirus are: Columbia University in New York; Intermountain Health Care, Inc. in Utah; the University of Pennsylvania; Washington University in St. Louis; Providence Health in Oregon; ProgenaBiome, a laboratory in California and Sanofi, a pharmaceutical company
In the journal "Antiviral Research," Dr. Xavier de Lamballerie and Franck Touret wrote that hydroxychloroquine is "considered to be safe and side-effects are generally mild and transitory," but that "the margin between the therapeutic and toxic dose is narrow
Warning: "the margin between the therapeutic and toxic dose is narrow. patients taking the drug have reported "life threatening and fatal" cardiac problems and "irreversible" vision problems.
By late March 2020, three potential antiviral therapies – favipiravir, remdesivir, and ritonavir – were in the final stage of human testing
Avigan (Anti-Flu Drug favipiravir)
The anti-flu drug Avigan (generic name favipiravir) won early approval in China for treating symptoms of COVID-19. It is also approved in Japan for investigational use into the novel coronavirus. Favipiravir was reported to help infected patients recover more quickly and with milder chest symptoms, according to Chinese officials. Still, parent company Fujifilm Pharmaceuticals, Japan has not yet confirmed the drug’s efficacy in treating COVID-19.
March 17, 2020, Chinese officials suggested that Favipiravir seemed to be effective in treating COVID-19 in Wuhan and Shenzhen.
The Chinese authorities, for example, consider Favipiravir to be a "clearly effective" antiviral drug which has been developed by the Japanese company Toyama Chemical, which named it Avigan, and has been tested by Wuhan University in China.
In a study of 240 patients with pneumonia, although not severe cases, this drug was given to half of them while the other half were given Umifenovir (or Arbidol), an antiviral used in Russia.
Those given Favipiravir saw that symptoms of fever and cough disappeared earlier but a similar number in each group ended up needing oxygen or respirators, concluding that Favipiravir was the "preferred" of the two drugs.
As reported in the MIT Technology Review, owned by the Massachusetts Institute of Technology (MIT), there have been few (and no conclusive) studies on the benefits of using certain compounds in the fight against coronavirus with Favipiravir and two others included
Why does Favipiravir work better?
Favipiravir is effective as it works by preventing the virus from copying its genetic material.
It was discovered while searching for drugs to treat a common flu and has strong inhibitory activity on RNA-polymerase RNA, which is dependent on most viruses with RNA genomes.
Among them, influenza viruses have been shown to be sensitive to this new antiviral drug, including strains with genetic resistance to neuraminidase inhibitors.
Favipiravir, the flu medicine which works against COVID-19
Avigan is only used when there is an outbreak of novel or re-emerging influenza virus infections in which other influenza antiviral drugs are either not effective or insufficiently effective.
https://www.google.com/amp/s/amp.marca.com/en/lifestyle/2020/04/10/5e90e6c722601d81378b4628.html
Influenza antiviral Avigan (favipiravir) to enter Phase III trials in COVID-19 patients
baricitinib
AI Uncovers a Potential Treatment for Covid-19 Patients
Software suggested an arthritis drug might quell an out-of-control immune response that damages the lungs. Now it's being tested in a clinical trial. They caught the attention of Eli Lilly, which markets the arthritis drug, known as baricitinib, under the brand name Olumiant.
Interferon Beta (Lung Disease Drug)
Another drug that showed promise fighting SARS, Interferon Beta is being tested for COVID-19. This antiviral drug is a common choice for doctors when the cause of an infection is unknown. It may inhibit replication of respiratory coronaviruses, and has shown promise fighting MERS in mice. Those mice studies showed that an injection of Interferon Beta within a day of MERS infection protected mice from death. This drug has also shown antiviral activity in combination with remdesivir.
Antibody Therapies (Blood Plasma)
Convalescent plasma, another experimental treatment for Covid-19, which is taken from people who were infected with Covid-19 but recovered. Plasma is the liquid part of blood, including proteins used for clotting, and when harvested from convalescents, it contains antibodies to the virus. So transfusing plasma from someone who recovered to someone who is sick could help them get better, or prevent them from getting sick in the first place.
The only antibody currently available for treating COVID-19 is found in the blood plasma of disease survivors. That's why the FDA and other federal agencies are investigating blood plasma therapies from recovered COVID-19 patients to treat the disease. These antibodies may be generated on a greater scale eventually, for instance by genetically engineered cows to produce the human antibody. But until that can be developed, human blood remains the only source.
COVID-19 Antibody Test (ELISA) for Those Already Infected With Coronavirus
Takeda already makes a medicine called intravenous immunoglobin, or IVIG, for treating patients who have immune disorders. It consists of antibodies of all types purified from the blood plasma of healthy people. Giving antibodies in this purified form is easier, because it requires a much lower volume of treatment; it’s safer, because there is no chance of transmitting other viruses; and it’s more efficient.
With its new treatment, TAK-888, Takeda hopes to create an IVIG from the blood of people who have been infected with the coronavirus and who have recovered. That could create a treatment or prophylactic relatively quickly. It might not need to go through phase I studies to demonstrate basic safety, or larger phase III studies to demonstrate efficacy. That means the treatment could be available sooner.
How blood plasma from recovered patients could help treat the new coronavirus
Kaletra (HIV drugs lopinavir and ritonavir)
The HIV drug Kaletra (generic names lopinavir and ritonavir) was studied early to great fanfare as a possible COVID-19 treatment. In theory, this medication could be helpful by reducing the viral load of those infected. It had been studied in the treatment of both SARS and MERS coronaviruses, but the studies were flawed. Unfortunately, an important study of 199 COVID-19 patients in China treated with this drug showed the pharmaceutical provided no additional benefit compared to standard care.
In 2020 lopinavir/ritonavir was found not to work in COVID-19
The biotech company Regeneron successfully developed an antibody drug to treat Ebola as well as one against MERS, a deadly coronavirus similar to Covid-19. Regeneron has an antibody drug that should enter human trials in June. Vir Biotechnology is also developing an antibody treatment for Covid-19 and says it could be ready for human trials this summer
COVID-19 drug development
https://en.m.wikipedia.org/wiki/COVID-19_drug_development
Coronavirus puts drug repurposing on the fast track
The biotech company Regeneron successfully developed an antibody drug to treat Ebola as well as one against MERS, a deadly coronavirus similar to Covid-19. Regeneron has an antibody drug that should enter human trials in June. Vir Biotechnology is also developing an antibody treatment for Covid-19 and says it could be ready for human trials this summer
Regeneron Boosts Production Capacity for COVID-19 Antibody Cocktail - quadruple production
Structure of Mpro from COVID-19 virus and discovery of its inhibitors
A new coronavirus (CoV) identified as COVID-19 virus is the etiological agent responsible for the 2019-2020 viral pneumonia outbreak that commenced in Wuhan1–4. Currently there are no targeted therapeutics and effective treatment options remain very limited. In order to rapidly discover lead compounds for clinical use, we initiated a program of combined structure-assisted drug design, virtual drug screening and high-throughput screening to identify new drug leads that target the COVID-19 virus main protease (Mpro). Mpro is a key CoV enzyme, which plays a pivotal role in mediating viral replication and transcription, making it an attractive drug target for this virus5,6. Here, we identified a mechanism-based inhibitor, N3, by computer-aided drug design and subsequently determined the crystal structure of COVID-19 virus Mpro in complex with this compound. Next, through a combination of structure-based virtual and high-throughput screening, we assayed over 10,000 compounds including approved drugs, drug candidates in clinical trials, and other pharmacologically active compounds as inhibitors of Mpro. Six of these compounds inhibited Mpro with IC50 values ranging from 0.67 to 21.4 μM. Ebselen also exhibited promising antiviral activity in cell-based assays. Our results demonstrate the efficacy of this screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases for which no specific drugs or vaccines are available
Summary: Six potential drug candidates have been identified as candidates to treat COVID-19 infections. The drugs, which have previously been subjected to clinical trials for treating a range of conditions, from arthritis to cancer, target Mpro, the main SARS-CoV-2 enzyme.
Source: University of Queensland
An international team of researchers has tested more than 10,000 compounds to identify six drug candidates that may help treat COVID-19.
The research, involving University of Queensland scientist Professor Luke Guddat, tested the efficacy of approved drugs, drug candidates in clinical trials and other compounds.
“Currently there are no targeted therapeutics or effective treatment options for COVID-19,” Professor Guddat said.
“In order to rapidly discover lead compounds for clinical use, we initiated a program of high-throughput drug screening, both in laboratories and also using the latest computer software to predict how different drugs bind to the virus.
Professor Guddat said the project targeted the main COVID-19 virus enzyme, known as the main protease or Mpro, which plays a pivotal role in mediating viral replication.
“This makes it an attractive drug target for this virus, and as people don’t naturally have this enzyme, compounds that target it are likely to have low toxicity.
“We add the drugs directly to the enzyme or to cell cultures growing the virus and assess how much of each compound is required to stop the enzyme from working or to kill the virus.
“If the amount is small, then we have a promising compound for further studies.”
After assaying thousands of drugs, researchers found of the six that appear to be effective in inhibiting the enzyme, one is of particular interest.
“We’re particularly looking at several leads that have been subjected to clinical trials including for the prevention and treatment of various disorders such as cardiovascular diseases, arthritis, stroke, atherosclerosis and cancer,” Professor Guddat said.
“Compounds that are already along the pipeline to drug discovery are preferred, as they can be further tested as antivirals at an accelerated rate compared to new drug leads that would have to go through this process from scratch.”
A graphic representation of how a discovered compound inhibits the COVID-19 virus main protease. The image is credited to Professor Luke Guddat.
After the enzyme’s structure was made public, the team received more than 300 requests for more information, even before the paper was published.
“To provide an analogy, we’ve provided scientists with a fishing pole, the line and the exact bait, and have in only one month caught some fish,” Professor Guddat said.
“Now it’s up to us and the other fisherman – our fellow scientists globally – to take full advantage of this breakthrough.”
“With continued and up-scaled efforts we are optimistic that new candidates can enter the COVID-19 drug discovery pipeline in the near future.”
COVID-19: Six drug candidates identified
Neuropilin-1 receptor helps virus infect cells
Specifically, this team showed that neuropilin-1 was critical for the SARS-CoV-2 virus to enter and infect cells.
By using an antibody to block one region of the neuropilin-1 receptor protein, the researchers showed that SARS-CoV-2 harvested from COVID-19 patients could not infect cells.
Moreover, cells lining the nasal passages from COVID-19 patients that were positive for neuropilin-1 were also positive for the Spike protein. These findings confirmed that Spike uses the neuropilin-1 protein to infect human cells in regions of the body where ACE2 isn’t present.
Daly and colleagues showed that SARS-CoV-2 was able to infect fewer cells if they used a small molecule called EG00229 or antibodies to block the Spike protein’s access to neuropilin-1.
Perhaps the most important implication is that the neuropilin-1 binding region of Spike should be targeted for COVID-19 prevention. Because a number of other human viruses, including Ebola, HIV-1 and highly virulent strains of avian influenza, also share this signature sequence of Spike, neuropilin-1 may be a promiscuous mediator of viral entry.
But it appears that the tango is not over yet. More dance partners have emerged. PIKFyve kinase and CD147 – two proteins – have also been shown to bind Spike and facilitate viral entry. Whether these new partners take center stage or play second fiddle to ACE2 and neuropilin-1 remains to be seen.
June 25 - 254 Treatments and 172 Vaccines
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