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Possible vaccines/treatment(s) for Coronavirus

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Sanofi, the maker of a branded hydroxychloroquine drug called Plaquenil, is producing as much as it can to help healthcare systems fighting the pandemic, CEO Paul Hudson told Reuters. But amid the manufacturing push, some employees are having to step aside if they show symptoms.

The company decided to “overproduce” drugs but is operating just under max capacity, Hudson added. That’s because the company sends workers who show symptoms—plus those who have come into contact with them—home for two weeks.
“One person getting a temperature means we lose maybe a half dozen people,” Hudson told Reuters.

On hydroxychloroquine, the highly touted drug that's taken center stage for its potential to treat patients with COVID-19, Sanofi is making as much as it possibly can, Hudson told the news service. The company started boosting production in February on the heels of Chinese data.

Sanofi has gotten requests for the drug from countries around the globe, and it's working with other suppliers to ensure even distribution, he added. Sanofi has the capacity to make millions of doses, according to the report.

As of Friday, global confirmed COVID-19 infections topped 1 million, and deaths passed 54,000

The pandemic has been playing out for months, and during that time, hydroxychloroquine—plus an older version, chloroquine—have garnered significant attention thanks to early anecdotal reports about their effects on COVID-19 patients and praise from President Donald Trump. The drugs have been approved for decades to treat malaria, lupus and arthritis.

Over the weekend, the FDA gave the drugs an emergency clearance, but European regulators this week decided against an approval until seeing more data. Some confusion and skepticism has stemmed from preliminary research in France, but the picture around the drugs in COVID-19 continues to evolve.

This week, researchers in Wuhan, China, published results (PDF) from a controlled study in 62 patients. The entire group received standard care, while half of the group also received hydroxychloroquine for five days.
In patients who received hydroxychloroquine, the time to clinical recovery and body temperature recovery were “significantly shortened," and those patients stopped coughing sooner, the authors said.
Only four patients progressed to severe illness; all were in the control group. Two patients in the hydroxychloroquine group experienced mild adverse reactions. The authors wrote that the drug “could significantly shorten [time to clinical recovery] and promote the absorption of pneumonia” in patients with COVID-19. More research is needed, the authors say.

“Considering that there is no better option at present, it is a promising practice to apply HCQ to COVID-19 under reasonable management,” the authors wrote. “However, large-scale clinical and basic research is still needed to clarify its specific mechanism and to continuously optimize the treatment plan.”
The result will “send a ripple of excitement out through the treating community,” Vanderbilt University infectious disease expert William Schaffner told The New York Times.

Demand for hydroxychloroquine has grown dramatically in recent weeks as a result of the attention. In a note Thursday, Bernstein analyst Ronny Gal wrote that the prescriptions for the drug had grown 500% in the last two weeks of March.

Drugmakers have been stepping up to provide supply. Novartis pledged a donation of up to 130 million global doses pending regulatory approvals. Mylan is ramping up production, and Teva and Amneal have each committed to making donations as well.
 
Nations with Mandatory TB Vaccines Show Fewer Coronavirus Deaths
New study finds a correlation, but clinical trials are still in progress

The preliminary study posted on medRxiv, a site for unpublished medical research, finds a correlation between countries that require citizens to get the bacillus Calmette-Guerin (BCG) vaccine and those showing fewer number of confirmed cases and deaths from Covid-19. Though only a correlation, clinicians in at least six countries are running trials that involve giving frontline health workers and elderly people the BCG vaccine to see whether it can indeed provide some level of protection against the new coronavirus.
Gonzalo Otazu, assistant professor at the New York Institute of Technology and lead author of the study, started working on the analysis after noticing the low number of cases in Japan. The country had reported some of the earliest confirmed cases of coronavirus outside of China and it hadn’t instituted lockdown measures like so many other countries have done.
from 02/04/2020 Nations with Mandatory TB Vaccines Show Fewer Coronavirus Deaths

To add
Among high-income countries showing large number of Covid-19 cases, the U.S. and Italy recommend BCG vaccines but only for people who might be at risk, whereas Germany, Spain, France and the U.K. used to have BCG vaccine policies but ended them years to decades ago. China, where the pandemic began, has a BCG vaccine policy but it wasn’t adhered to very well before 1976, Otazu said. Countries including Japan and South Korea, which have managed to control the disease, have universal BCG vaccine policies.

Early days, but interesting I hope.

Cross posted from the worldwide thread
 
One of the oldest forms of immunotherapy is being pressed into action again. A study in JAMA follows the transfer of serum from five donors who had recovered from the respiratory disease COVID-19 and had high titers of immunoglobulin G antibodies to the causative coronavirus SARS-CoV-2 to five patients on mechanical ventilation. Three of the five recipients were weaned from assisted ventilation and were subsequently discharged. The study has many limitations beyond the small number of patients, including the lack of a placebo group and the diverse set of treatments, including antivirals, that each patient was receiving.
from 03/04/2020 COVID-19 Research in Brief: 28 March to 3 April, 2020

cross posted from worldwide thread
 
Early days, but interesting I hope.

Its interesting but from what we've seen so far I'm not sure I expect the effect to be that strong. Because the UK still gave these vaccines routinely till 2005, and France gave them until 2007.
 
Its interesting but from what we've seen so far I'm not sure I expect the effect to be that strong. Because the UK still gave these vaccines routinely till 2005, and France gave them until 2007.
Yes, I was wondering about that, most people in my age group had the BCG
 
Three interesting articles from the Lancet

Preventing COVID-19-induced pneumonia with anticytokine therapy
Morbidity and mortality associated with COVID-19 are highest in the elderly and among people with comorbidities. Individuals with comorbidities could theoretically include patients with immune-mediated disorders taking cytokine blockers, as these drugs inhibit the function of molecules involved in the host defence against pathogens. Surprisingly, however, no increase of SARS-CoV-2-driven pneumonia has been documented in such patients so far. Therefore, the question arises as to whether patients with immune-mediated disorders on cytokine inhibitors represent a privileged group who are resistant to COVID-19 disease. Analysis of the cytokine profile characterising severe cases of COVID-19 suggests this assumption might be the case.
from 06/04/2020 https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30092-8/fulltext

Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations
As coronavirus disease 2019 (COVID-19) spreads across the world, the intensive care unit (ICU) community must prepare for the challenges associated with this pandemic. Streamlining of workflows for rapid diagnosis and isolation, clinical management, and infection prevention will matter not only to patients with COVID-19, but also to health-care workers and other patients who are at risk from nosocomial transmission.
from 06/04/2020 https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30161-2/fulltext

Understanding pathways to death in patients with COVID-19
Since the first cases of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were identified in China in December, 2019, we have witnessed increasing numbers of infections and associated deaths worldwide. Although the case fatality rate for SARS-CoV-2 infection (ie, the total number of deaths in patients positive for SARS-CoV-2 divided by the total number of people with a positive test) is not high, given the huge scale of the pandemic, the actual numbers of deaths are considerable.
from 06/04/2020 https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30165-X/fulltext
 
Three interesting articles from the Lancet

Preventing COVID-19-induced pneumonia with anticytokine therapy

from 06/04/2020 https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30092-8/fulltext

Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations

from 06/04/2020 https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30161-2/fulltext

Understanding pathways to death in patients with COVID-19

from 06/04/2020 https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30165-X/fulltext

Ive been reading a lot about this, purely for selfish reasons as my youngest son is on a cytokine inhibitor for RA and AS.

It would seem that although he may be at increased risk of catching covid-19, he may have less chance of it killing him.

He's using IL7 , and there's not much information because it's a trial at present ( for his condition not C19) but I get how it could stop the pneumonia, by stopping an immune response.
 
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This isn't a treatment but I thought it belonged in this thread better than others.

Consumer tech converted to rapidly test for Covid-19
A consumer DNA testing device dubbed DnaNudge has been modified to provide a rapid, lab-free PCR (polymerase chain reaction) test that detects COVID-19 and delivers results in just over an hour.
..
Experts at Imperial College Healthcare NHS Trust are working with the Imperial College London and DnaNudge team to enable the new test to be applied to patients and staff if it continues to prove successful.
According to Imperial College a key advantage of DnaNudge’s solution is that the RNA polymerase chain reaction (PCR) test requires no sample handling and is able to deliver processing outside of a laboratory environment – using DnaNudge’s patented and miniaturised NudgeBox analyser.
from 14/04/2020 Consumer tech converted to rapidly test for Covid-19 | The Engineer
 
This sounds promising, too:


The immune system normally uses proteins called cytokines as weapons in fighting a disease. For unknown reasons in some COVID-19 patients, the immune system first fails to respond quickly enough and then floods the body with cytokines, destroying blood vessels and filling the lungs with fluid.

The doctors tried a drug called Actemra, which was designed to treat rheumatoid arthritis but also approved in 2017 to treat cytokine storms in cancer patients.

“Our role was to quiet the storm,” said Dr. Samuel Youssef, a cardiac surgeon. “Dr. Padgett was able to clear the virus” once his immune system was back in balance.

Dr. Matt Hartman, a cardiologist, said that after four days on the immunosuppressive drug, supplemented by high-dose vitamin C and other therapies, the level of oxygen in Padgett’s blood improved dramatically. On March 23, doctors were able to take him off life support.

Four days later, they removed his breathing tube. He slowly came out of his sedated coma, at first imagining that he was in the top floor of the Space Needle converted to a COVID ward.

Mind you they've also said that viagra is a possible treatment :)
 
Some more detail on remdesivir status

After dribs and drabs surfacing about Gilead Sciences' COVID-19 hopeful, remdesivir, the first data from a placebo-controlled study are here—at least, an early look at them. Remdesivir cut recovery time for hospitalized COVID-19 patients by four days, or 31%, in a National Institutes of Health-sponsored study pitting the drug against placebo in more than 1,000 patients.

Based on the results, the FDA could greenlight remdesivir for emergency use as early as Wednesday, a senior administration official said, according to The New York Times.
“Although a 31% improvement does not seem like a knockout 100%, it is a very important proof of concept because what it has proven is that a drug can block this virus,” Anthony Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), said during a White House briefing with reporters Wednesday.

The study, carried out at 68 sites around the world, defined “recovery” as being healthy enough to leave the hospital or return to normal activity level. The trial wasn’t reserved for the sickest of patients—unlike other trials that only included patients with “severe” disease—but the patients still had to be hospitalized with confirmed COVID-19 infection along with “evidence of lung involvement,” like the need for supplemental oxygen or mechanical ventilation. The study did not include patients with milder, coldlike symptoms or those who were asymptomatic.

The results also “suggested a survival benefit,” with a death rate of 8% in patients who received remdesivir and 11% in those who got placebo, NIAID said in a statement. The numbers were too close to be statistically significant, Fauci said, but the data need to be further analyzed and undergo peer review. Gilead is also testing remdesivir in moderately ill patients.

Multiple analysts, meanwhile, used the same metaphor Wednesday to describe the limitations of remdesivir. “The bottom line is the drug improves patients and clearly appears to help,” wrote Jefferies analyst Michael Yee in an investor note. “It’s not a magic silver bullet but it does improve patients and likely will get broader uptake.”
Evercore ISI analyst Umer Raffat considered the data alongside results from other studies, including a Gilead-sponsored trial testing a five-day course and a 10-day course of remdesivir—with no control arm—as well as a study conducted in China.

“Totality of data… suggests remdesivir ‘works’, but it’s not a silver bullet,” Raffat wrote. But Fauci doesn’t see remdesivir, an experimental antiviral initially developed for Ebola, as a silver bullet. Rather, he sees it as a steppingstone to better treatments that could even be combined for a greater effect.
 
Possibly the most random covid development of the week...

When llamas encounter pathogens like viruses and bacteria, their immune systems fight them off with two weapons: antibodies much like those made by the human body and much smaller antibodies called single-domain antibodies or “nanobodies.” Now, those nanobodies have inspired a potential treatment for COVID-19 that may be able to be delivered straight to the lungs, where the virus tends to set up shop.

Scientists from the University of Texas (UT) at Austin, the National Institutes of Health and Ghent University in Belgium developed a treatment that links two nanobodies isolated from a llama to create an antibody that binds to the spike protein on the coronavirus that causes COVID-19. That bond prevented the virus from invading cells, the researchers reported (PDF) in the journal Cell.
The researchers actually started working on the treatment in 2016, when they were studying two related coronaviruses, SARS-CoV-1 and MERS-CoV. They injected a llama named Winter with spike proteins from the viruses. Six weeks later, they collected her blood and isolated antibodies that had bound to the protein.

After SARS-CoV-2 emerged, sparking the COVID-19 pandemic, the scientists built on their earlier experiment, linking two copies of the llama nanobody that had worked against SARS-CoV-1. Now that they’ve shown the engineered antibody can neutralize the new virus in cell cultures, they’re planning preclinical studies in rodents and nonhuman primates.

Llamas and other members of the camelid family have long been of interest to medical researchers because of the single-domain antibodies they produce. In 2018, for example, a scientific team including Scripps Research Institute and Janssen scientists described an experimental flu vaccine they developed by immunizing llamas against the flu and then isolating broadly neutralizing single-domain antibodies (sdAbs) from them. Because the sdAbs target a region of the virus that doesn’t mutate, the researchers believe a llama-inspired vaccine could offer more universal protection than standard seasonal flu vaccines do.

Camelids have also inspired experimental treatments for cancer and multiple sclerosis that capitalize on the tendency of the antibodies to bind more tightly to therapeutic targets than human-inspired antibodies can.
Another advantage of llama nanobodies is their size, said Daniel Wrapp, a graduate student at UT Austin and co-author of the new paper. They’re about a quarter of the size of human antibodies—small enough to be nebulized and delivered straight to the lungs via an inhaler. "That makes them potentially really interesting as a drug for a respiratory pathogen because you're delivering it right to the site of infection," Wrapp said in a statement.
 
Three interesting articles from the Lancet

Preventing COVID-19-induced pneumonia with anticytokine therapy

from 06/04/2020 https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30092-8/fulltext

Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations

from 06/04/2020 https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30161-2/fulltext

Understanding pathways to death in patients with COVID-19

from 06/04/2020 https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30165-X/fulltext

blimey. I’m on golumimab (well was until my last injection which was in February)

very interesting reading
 
Remdesevir is getting a lot of press recently but there is a whole host of existing medicines being clinically trialled.

As April waned, Amgen announced it would take PDE4-inhibitor Otezla, which it picked up from Celgene last year, into a clinical trial soon to study its effectiveness in preventing respiratory distress from COVID-19.

Meanwhile, Novartis plans to evaluate IL-1beta blocker Ilaris to treat cytokine storm, a severe overimmune reaction that can be fatal. Investigators will primarily focus on whether Ilaris can keep patients off ventilators. Top-line results are expected late summer.

Novartis is also evaluating IL-17A inhibitor Cosentyx, leukemia drug Gleevec, old heart drug Diovan(valsartan) and asthma therapy Xolair for their effects on COVID-19.

Meanwhile, the Swiss drugmaker and its partner Incyte have commenced a study for JAK inhibitor Jakafi to treat cytokine storm. The blinded, double-arm study will test Jakafi alongside standard-of-care therapy in COVID-19 patients with pneumonia.

Eli Lilly took rheumatoid arthritis med Olumiant into clinical trials as well, announcing in mid-April it would launch a U.S. trial immediately and later expand testing to Europe and Asia. The project started in February when Benevolent AI identified the Lilly drug as a possible treatment, not only for its anti-inflammatory effects, but also potential antiviral activity.

AstraZeneca rolled out a test of blood cancer med Calquence in mid-April, after NIH researchers observed “some clinical benefit” in COVID-19. But most recently, AZ said it would launch a trial for diabetes superstar Farxiga. The Dare-19 trial will study Farxiga alongside supportive care, focusing on its potential for reducing the progression of COVID-19 symptoms and cutting the risk of clinical complications and death.

After initially planning to evaluate blockbuster Soliris' effect on COVID-19, Alexion pivoted last month and said it would put follow-up drug Ultomiris into a phase 3 clinical trial instead. Alexion cited preclinical data showing the drug's mechanism could lower cytokine and chemokine levels, plus reduce lung inflammation.

Finally, a suite of IL-6 inhibitors have been pitted against COVID-19, including Sanofi and Regeneron's Kevzara, Roche's Actemra and EUSA Pharma's Sylvant.

And some early results are in: In late April, Sanofi and Regeneron cut severely ill patients from the phase 3 U.S. trial of Kevzara after a precursor study showed negligible results in treating those patients requiring oxygen therapy, but not more intensive treatment. It'll focus on critically ill patients instead.

Roche's Actemra, meanwhile, posted an early trial win late last month in a small-scale French study, showing it could help combat cytokine storm in severe and critically ill COVID-19 patients with pneumonia.

A number of big-time generics players––including Bayer, Mylan and Novartis––have donated millions of doses of antimalarial hydroxychloroquine to hospitals and clinical trials despite some iffy evidence on its use to treat COVID-19. A favorite of President Donald J. Trump, hydroxychloroquine recently flopped a VA study in late April and has been treated with caution by global health authorities.
 
Gilead Sciences has captured worldwide attention since its antiviral drug remdesivir was approved late last week as the first therapy to treat COVID-19. Now, as bad actors target companies at the head of the spear in the novel coronavirus response, Gilead might have found itself in their sights.

Gilead was recently hit with an Iranian "password spraying" attack that used fake email login pages in an attempt to access passwords of high-ranking executives, Reuters reported.

In April, an Iranian hacker group known as "Charming Kitten" sent an email, purportedly from a journalist, to a Gilead legal and corporate affairs executive as part of a scheme to compromise the drugmaker's company email accounts, three cybersecurity experts told Reuters.

Iran's mission to the United Nations denied the country's involvement in the scheme. Reuters wasn't able to confirm whether the attack was successful.

Earlier this week, the U.K. and U.S. governments warned that "malicious cyber campaigns" were targeting healthcare policymakers and researchers to gain access to corporate emails using "password spraying," or using common passwords to access a number of accounts.

Gilead has been the focus of intense international scrutiny since its remdesivir won emergency clearance from the FDA last week. The drug is the only new therapy so far authorized to treat COVID-19.

The company has said it would donate its entire existing supply, or about 1.5 million doses, to the U.S. government for distribution. The Trump administration has shipped about 32,000 doses to Indiana, Massachusetts, New Jersey, New York, Rhode Island, Tennessee and Virginia, Axios reports.

With the emergency approval, Gilead has worked to increase its own supply of the medicine and is in licensing talks with some of the “world’s leading chemical and pharmaceutical manufacturing companies” about their ability to produce remdesivir for countries in Europe, Asia and beyond until at least 2022.

The company is discussing licensing the med to generics makers in India and Pakistan to supply patients in developing countries. It's also considering licensing the drug to the Medicines Patent Pool and exploring using UNICEF’s expertise for distribution in low- and middle-income countries.
 
Moderna post.positive first results for their vaccine

 
So Remdesivir initial results showed some promise but it obviously isn’t the final answer as a covid medicine.

Roche are now initiating phase 3 clinical trials for a combination product containing Remdesivir and a drug called Actemra which acts against cytokine storms. It’ll be interesting to see how this goes with severe covid patients.

 
How is the vaccine going then? The government spokescunts seems pretty bullish about it.

The track and trace seems to be slow off the mark and the app is a month away so the vaccine would be something to cheer the mood :)
 
Latest vaccine news. Long read...

British drugmaker AstraZeneca has made clear its intent to rapidly scale production of Oxford University's COVID-19 vaccine hopeful despite a dearth of clinical data to support its use. Now, with an eye-popping deal worth three-quarters of a billion dollars, AstraZeneca is putting its money where its mouth is.

The British pharma has inked a $750 million deal with the Coalition for Epidemic Preparedness Innovations (CEPI) and Gavi, the Vaccine Alliance to manufacture and distribute 300 million doses of Oxford's adenovirus-based COVID-19 vaccine by the end of 2020, the drugmaker said Thursday.
AZ also agreed to a licensing deal with the Serum Institute of India to provide 1 billion doses of the vaccine to low- and middle-income countries, with the goal of 400 million produced by year's end.

In total, the deals will bring AstraZeneca's overall supply capacity for Oxford's vaccine candidate to more than 2 billion doses per year, the drugmaker said. The agreement will task CEPI with manufacturing the vaccine, while Gavi will handle procurement.

The marketing effort will be overseen by the Bill and Melinda Gates Foundation's and World Health Organization's Access to COVID-19 Tools Accelerator, which will "ensure the fair allocation and distribution of the vaccine across the world," according to a release.

AstraZeneca's enormous manufacturing and distribution layout represents the single largest effort so far to pump hundreds of millions of doses of a COVID-19 vaccine hopeful onto the market before the end of 2020.

AstraZeneca reached an agreement with Oxford in April to manufacture and commercialize hundreds of millions of doses of its COVID-19 vaccine as health regulators around the world scrambled to meet what will likely be global demand.

The vaccine, dubbed AZD1222, contains the genetic material of the SARS-CoV-2 spike protein. It isn’t replicating, so it can’t cause an ongoing infection in recipients, AZ says. The company hopes the vaccine can deliver a strong immune response from one dose by triggering the body to produce the spike protein and attack the novel coronavirus upon infection.

In late May, AstraZeneca scored a $1.2 billion contribution from the U.S. for development, production and delivery of its potential shot starting this fall. The company has signed up to deliver 400 million doses through its initial supply agreements, including a 300-million-dose work order for the U.S. and 100 million doses for the U.K.

In a more minor move last week, AstraZeneca and Oxford BioMedica inked a one-year deal covering "multiple batches" of the vaccine.
As part of the agreement, AstraZeneca will have access to Oxford BioMedica's 84,000-square-foot OxBox commercial manufacturing center in Oxford, England. The agreement will turn out most of the clinical and commercial supply in 2020 with the possibility of expansion in the future, Oxford BioMedica said in a release.

AstraZeneca's massive supply commitments will depend on results from an ongoing phase 2/3 trial of the vaccine that hopes to enroll 10,260 people in the U.K. The study aims to generate results to support the first shipments to customers in September. A 1,000-patient phase 1 trial hasn't yet turned out top-line data.

The phase 2 test will relax exclusion criteria used in phase 1, notably by enrolling a small number of children ages 5 to 12 and adults age 56 and older. One cohort will enroll adults over 70, a demographic that is particularly at risk from the coronavirus. By expanding the age range, the researchers aim to understand how immune response varies across demographic groups.

Once the vaccine moves into phase 3, the researchers will limit enrollment to people age 18 and older. Adult participants in the phase 2 and 3 trials will be randomized to receive one or two doses of AZD1222 or a vaccine against meningococcal bacteria that will serve as the control.
 
I'm getting the general impression that some sort of effective treatment of Covid-19 is much more of an optimistic prospect (and could possibly become available a fair bit sooner) than an effective vaccine any time soon.

Do the more science-together people agree?

Cheers :)
 
I'm getting the general impression that some sort of effective treatment of Covid-19 is much more of an optimistic prospect (and could possibly become available a fair bit sooner) than an effective vaccine any time soon.

Do the more science-together people agree?

Cheers :)

I don't think so personally. A cocktail of the current candidate drugs may well help significantly but I think it'll take years to find a 'proper' treatment drug.

The current drugs are all repurposed products. This means a lot of the groundwork with respect to drug development and safety has already been done. A proper targeted drug will need to be designed and developed from scratch and that will take longer than the current virus development programmes.
 
I don't think so personally. A cocktail of the current candidate drugs may well help significantly but I think it'll take years to find a 'proper' treatment drug.

The current drugs are all repurposed products. This means a lot of the groundwork with respect to drug development and safety has already been done. A proper targeted drug will need to be designed and developed from scratch and that will take longer than the current virus development programmes.

Thanks -- I was not doubt being too unrealistic :(

I will take away the words 'may well help significantly' from your post though </crosses fingers ;) >
 
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