Anti-viral drugs Covid-19

If a new vaccine can be developed in under a year, why not an effective antiviral drug?

An effective drug that could treat a person once infected with Covid-19 and prevent the potential serious consequences would clearly dramatically reduce the impact of the pandemic. Indeed, if there was a very effective and very safe drug, we wouldn’t need to worry about a new vaccine!  It is also reasonable to ask that as new vaccines have been developed within 12 months from start to finish, can we be similarly optimistic about new treatments?

Do we actually need a new drug?

  • As the Christmas panto season happens (or not this year!), what does the story of Aladdin tell us about prospects of new drugs for Covid-19?
  • At the beginning of the pandemic there was an important question to be asked about treating Covid-19: “Can any drugs already licensed for treating other viral infection or indeed other diseases, be successful against Covid-19?
  • In technical terms – can we repurpose existing drugs rather than the much longer and risker process of developing new drugs?

In this post, I review where we are up to in repurposing and point out the challenges in starting to develop completely new drugs.

What do we want an antiviral drug to do for Covid-19?

  • There are two ways any antiviral drug might work- by preventing
    • the virus multiplying once it enters a human cell
    • the damage after the virus has multiplied resulting in part as a consequence of the  body’s defence mechanisms 
  • As the second of these  is common to a whole range of  infections (and indeed immune diseases like rheumatoid arthritis), repurposing a range of existing drugs was worthwhile trying in Covid-19
  • The best example of this was the trial of the steroid dexamethasone, which has significantly cut the death rate of seriously ill Covid-19 patients
  • The rest of this post will focus on specific antiviral drugs to stop the virus multiplying. 
  • These could then be given to people in the community at the first signs of infection
  • How likely is it that there are such existing drugs that could do this for Covid-19?

What examples are there of drugs that stop other viruses multiplying?

  • The best example is in HIV/AIDS. Indeed, the so called anti-retroviral treatments are the mainstay of AIDS management (there is no vaccine for this infection) and have dramatically improved the outcome
  • Actually, there are around 24 drugs that stop the HIV virus multiplying
  • There need to be so many as patients get resistant to individual drugs and combinations of different agents work better than single drugs
  • You may remember during the Swine Flu H1N1 epidemic there was much enthusiasm for the antiviral drugs Tamiflu and Relenza that we’re widely prescribed in primary care
    • In truth the infection turned out to be not as serious as was feared
    • The only difference was a modest reduction in the number of days people felt ill for and indeed recent analyses have suggested they weren’t that effective 
  • This all suggests that antiviral drugs make sense as a concept but there was no evidence that drugs which worked for one virus would necessarily work for other viruses

What about using existing antiviral drugs for Covid-19?

  • Lots of have been tried!
  • There are a vast number of trials investigating a whole range of existing antiviral drugs for Covid-19
  • I searched the available databases yesterday and found this!
  • The only drug thus far with any positive data is remdesivir
    • There was initial enthusiasm for this drug as a specific antiviral agent for Covid-19 19
    • It had been developed for use against other corona viruses eg  SARS
    • Some data suggested it could make a modest difference to how long people had symptoms 
    • The USA was very enthusiastic and, looking after their own interests, went out shopping!
    • Although there have been many trials, the most recent data suggest the benefit from remdesivir is minor and it is not a candidate for widespread use

How easy will it be to develop a new drug from scratch?

It is simplest to divide up the process into stages:

  • The early laboratory work for identifying a possible drug
  • Testing the drug in animals
  • Testing the drug in humans
  • There is a considerable drop out at each stage (one estimate is that only 0.5-1% of all drugs  tested in animals end up being marketed for human use)
  • The full process takes on average 10-15 years
  • What it costs is obviously variable, but a reasonable average for recently licensed  drugs is between $1-2bn
  • Developing drugs is a risky business!

What are the risks?

There are clinical and commercial risks.  I have put these in a reasonably sensible order, but for example evidence of harm can emerge at any stage, which would at that point stop the drug being developed further or sold

  • Drug doesn’t work
  • Drug works but proves to be harmful
  • Early investors lose confidence and development stops
  • Drug works but gets overtaken by better/cheaper drugs
  • Technical problems in production etc
  • Disease stops being a problem so sales plummet

Who takes the risk?

  • Conventionally this has been the big pharmaceutical companies
  • However much more common these days is for ‘big pharma’ to enter into the process some way down the line and pay a reasonable premium for a license to develop a drug further 
    • After university researchers have shown there may be a promising future for something they have discovered
    • When a small biotech company, perhaps set up by a university specifically to further develop their discovery, has shown benefit in animal testing
  • To get to the stage, individual researchers, universities and small companies may seek external speculative investors or use their own funds (including researchers remortgaging their own homes!)

Should this not be different for a global pandemic like Covid-19? 

  • It has been easy getting billions for vaccine development 
  • By contrast, governments and other organisations have only funded $millions (not billions) into research for new drug treatments
  • There has to be some shared risk/reward for companies to make the size of investment that is needed

Is there any possibility of speeding up/making the development process cheaper and quicker ?

  • Again, the short answer is that the pace of change in drug development is staggering
  • Use of artificial intelligence (* see my post on protein structures) has meant that the very lengthy development stages can be reduced in time and screen thousands of potential drugs very quickly so that clinical development can focus on the most likely 
  • The clinical testing period which has up to now been say 5-10 years can also be reduced as has been demonstrated by the speed at which vaccines have been brought to market
  • There is one major difference between vaccines and other drugs in that the mechanism of vaccines – to enhance the body’s production of its own antibodies – is generally known to be successful and safe
  • For drugs designed for new treatment, this is more speculative



  • It would have been great to have reached the end of this difficult year with exciting news of a successful new antiviral drug to match the success of vaccines
  • Of course, if the vaccines are successful and provide long term protection, then new treatments may not be needed
  • However, we should be reassured that such development is happening (albeit more slowly) but also could make us better able to cope with the next viral pandemic

And finally!

This will be my last post this year.  Thanks for all the positive comments and the interest across so may countries.  Hopefully our governments will be better able or willing to ‘follow the science’ in 2021!

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Anti-viral drugs Immunity Outcome transmission

Genetic mutations in the virus and in humans: Do they offer a way out?

As the pandemic progresses the virus mutates. Mutations in us result in differences in how our immune system fights the infection. In this post I review how recent research on the impacts of these mutations could change the way we control and treat the disease – I found the results really interesting and even hopeful!

What is a mutation?

  • The different genes in every organism, from virus to man, consist of chains of different sequences of 4 building blocks, called nucleotides
  • The 4 – referred to as ‘A’, ‘C’ ‘G’ and ‘T’- can form very long sequences with up to 2 million in  any one gene 
  • You can think of genes as very long necklaces made up of Lego blocks in the 4 main colours
  • The exact sequence of the nucleotides in each individual gene does vary:
    • no two humans have identical sequences in any of our genes: there are many points of difference
    • even though a virus has far fewer and much shorter genes, there can be many differences in the genes (these are then referred to as different ‘strains’)
  • Such differences in the sequence of nucleotides are referred to as mutations. Mutations continually occur in all species
  • In some mutations, there is a substitution of one nucleotide for another
    • In the example below a  ‘red’ T was substituted by a ‘blue’ ‘C’
  • In other mutations, sequences can be missing from one gene to another: this is called deletion
  • In yet other mutations, extra sequences can be added, often copies of short sequences, this is called duplication

How common are mutations in the Covid-19 virus?

  • This virus just has one strand of the genetic material RNA
  • This strand though has 30,000 nucleotides
  • Already scientists have identified 13,000 separate mutations 
  • Although this might seem very high, the level of mutations is 6 times lower than in the influenza virus 

What are the potential consequences of Covid-19 mutations?

  • Most mutations will have no consequences in terms of the infection
  • Even so, identifying such individual mutations can be very helpful in tracking the spread of infection between people
  • Of those that do make a difference, some mutations can affect the transmissibility of the virus (ie how easily it spreads) and others the severity of the infection
  • Early on in the pandemic, one mutation (OK it’s called D614G) was thought to be responsible for altering the spike protein on the surface of the virus that causes it to stick to human cells (and is the bit that most vaccines are directed against)
  • This mutation is now present in 80% of Covid-19 virus samples studied
  • The Chilean outbreak is thought to be due to further mutations in the spike protein gene making it even more sticky to human cells
  • There are other mutations, associated with a deletion of some of the virus’s genetic sequence, that make it less infectious
  • A study from Singapore in the Lancet in August suggested that that country’s lower death rate may be due to a deletion which produces less severe disease

The results were impressive-Singapore has lowest fatality rate in the world:

  • What is interesting is that mutations in the virus are likely to occur in response to how humans combat the infection.  There could be both beneficial and harmful consequences:
    • Beneficial: Consider for example there are two mutations: the one that causes very serious infections and the other that causes mild infection.  People carrying the latter are more likely to spread the infection and thus that version of the virus will become more prevalent.
    • Harmful: There are several examples of  viruses mutating to try and overcome our body’s immune response
  • We should not forget that significant (but what significant means is difficult to be precise) mutations in the virus could affect the success or otherwise of any new vaccine
  • Although at the moment most vaccine researchers believe their vaccines should be resilient against the types of mutation currently recognised  

How common are mutations in humans?

  • The answer of course is immensely common, each one of us probably has millions of mutations
  • Many of these mutations affect how our immune systems fight infections
  • The interesting question is therefore to ask if mutations in these immune genes explain why some people have more serious infections than others
  • The short answer from a vast number of research studies is yes:  differences in these genes between people are linked to various dimensions of the outcome, including mortality
  • An example of a recent study is the one referred to below from the USA that showed that some people have a mutation that reduces the body’s production of interferon, which is our natural anti-viral drug. 
  • Indeed, other studies have shown that an effective interferon response is necessary to fight this virus
  • To be honest, at first sight knowing that people who have more severe disease than others have a genetic basis for this might seem not that helpful, as we cannot change our genes
  • But what this kind of research can do is to help suggest new drug possibilities.  Just yesterday came a press release from the biotech company ILC Therapeutics for an inhaled version of interferon that might be a useful new drug
  • This follow from another small UK study in July of the use of another type of  interferon which showed an 80% reduction in the likelihood of severe complications
  • These are early days and more evidence is needed


  • There has been a massive amount of research into the genes that:
    • allow Covid-19 to invade and cause such mayhem
    • impact on our immune response 
  • None of the research findings individually will be a game changer, there is a very complex jigsaw of how all the pieces fit together 
  • A better understanding of the mutations in the virus can help in tracking the infection both over time and between regions and local outbreaks
  • More importantly these insights from genetic mutations can help focus attention on novel approaches to treating the infection    

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Anti-viral drugs

A possible new treatment for Covid-19

Up to now there have been no effective treatments that can get rid of the coronavirus that causes infection. Yesterday there was an announcement in the UK that a trial had started of a promising new drug – which is a ‘monoclonal antibody’.  In this post I discuss the science behind this drug, what the current situation is and what are the prospects for its future success.


  • As widely discussed in this blog, one of the keys to successful treatment of Covid-19  is blocking with antibodies the spike protein that the virus uses to get into our cells
  • Following infection, affected people develop antibodies naturally, which do wane over time but hopefully will protect against a subsequent infection
  • Indeed, some patients, who have been very ill, produce large amounts of antibodies and have been giving donations of their plasma, which can then be used to treat seriously ill patients
  • This is a labour intensive and costly procedure, and cannot easily be scaled up for mass use.  It is also not clear how effective it is in the most ill patients
  • The vaccines that are being developed also aim to stimulate the body to produce natural antibodies that will provide protection; but again the time it takes for  the antibody response means that vaccines cannot be used as a treatment.
  • The obvious next step is to produce the antibody as ‘a drug’ which can be injected into patients when they become ill or even are known to have had contact with the virus
  • Antibodies can now be manufactured for use in this way and are referred to as monoclonal antibodies.  The ‘monoclonal’ means that they are very ‘pure’ and have very specific targets
  • These manufactured antibodies can be more powerful than natural antibodies

Is this a new technology?

  • Absolutely not!
  • There are a vast number of monoclonal antibodies manufactured and used by millions of patients worldwide
  • They have transformed the treatment of many cancers and also immune disorders such as rheumatoid arthritis
  • Indeed,  one of the world’s largest selling drugs is adalimumab, used to treat  rheumatoid arthritis, which has annual global sales of $20 billion
  • I helped lead a worldwide effort to examine the safety of these drugs following their introduction in around 2000

What is the technology for Covid-19? 

  • The US biotech company Regeneron has produced two monoclonal antibodies against the spike protein and combined them as REGN-COV2 – a dual antibody cocktail
  • This is an interesting design approach, and makes sense as proteins  are complex structures so there are several places one can select for an antibody to attach itself.
  • In animal studies the Regeneron cocktail was successful in reducing the level of virus, and the severity of pneumonia, in affected monkeys, but did not completely eliminate the pneumonia
  • Other companies are also working to develop further monoclonals, including the UK’s AstraZeneca (which is also producing the Oxford vaccine)

The clinical trial programme

  • Regeneron has started two trials in the USA
  • These trials will assess the safety, how well the injection is tolerated and how it affects outcome in patients with Covid-19
  • Interestingly one of these trials is also recruiting people who are asymptomatic but who have the virus – presumably to see if the injection prevents them becoming ill
  • Yesterday (September 14th) it was announced that the UK study of different treatments for Covid-19 in hospitalised patients – The Recovery Trial – would also start researching whether this antibody cocktail works

Should we get excited?

  • The technology has been incredibly successful in cancers and other diseases, so obviously worth trying in Covid-19 
  • We don’t know yet if these (or indeed other) monoclonals will be effective in stopping the disease and at which stage they should be used
  • We also don’t know whether one dose will be enough (the Regeneron trials are only of a single shot)
  • There may be significant side effects – though other monoclonal drugs are generally safe and well tolerated
  • They are not cheap to produce.  It is a complete guess but, based on other monoclonal drugs, a single shot might cost £1000.
  • The challenge will be therefore finding the appropriate target group:
    • It will be too expensive and difficult to produce in sufficient quantities to give to asymptomatic people
    • It might not be effective to give it when people are already quite ill with pneumonia 


  • Development of this antibody cocktail is welcomed and might be the best hope of a truly effective anti-viral drug for Covid-19
  • At this stage we need to be realistic as to what contribution we can expect it to make to reducing the impact of the epidemic

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Anti-viral drugs Covid-19

Could drugs be a solution to the virus?

Covid-19 would be less of a worry if there was a very effective treatment

It is an obvious fact that the world might not worry about the dangers of catching Covid-19 if there was an effective and safe (and hopefully cheap) drug to stop the disease ‘in its tracks’. The idea is that it could be taken when people  had the very first minor symptoms of being unwell or even when testing positive.  As a  historical parallel, in the pre-antibiotic era, infections that we now consider minor such as ear infections and sore throats could have led to life threatening complications.  The population now, though, no longer worries about such disorders because antibiotics are so effective (although the major concern of antibiotic resistance is real).  This post thus addresses how likely is it that we could get such antiviral drugs that could be similarly effective and appropriate for widespread use in Covid-19.

Comparison with antibiotics The comparison with antibiotics and bacterial infections is interesting.  In most countries those who visit their general practitioner with a  sore throat or a chest infection these days would be denied antibiotics:  the advice being that (without testing)  the illness (a) is due to ‘a virus’ and hence  does not respond to antibiotics and (b) will settle down on its own.  Thus, we have developed an acceptance  that common viral infections do not  need specific treatment and are not likely to become serious.  Covid-19 has proved the latter to be untrue, so where are we on the path to addressing the former? 

When might drugs be used in Covid-19? Drugs might be used at 3 stages

  • To stop people becoming infected after being exposed to the virus 
  • To stop the virus actively producing many copies of itself in the body and prevent severe clinical problems
  • To treat the ongoing clinical problems, and especially the complications, caused by the virus

Vaccines cover the first stage. Drugs for the third stage cover the range of drugs from simple agents that control symptoms such as paracetamol, to those used to treat and control the serious consequences and the complications of infections.  (Drugs in this class include dexamethasone that received much publicity recently as it reduced the number of deaths in Covid-19 patients admitted to intensive care units.)  

What is lacking are drugs that stop the virus, once it has established itself, from causing further harm.  Viruses work by entering our cells and then taking them over and using them to produce millions of copies of themselves.    If that process can be stopped, then if someone became infected the virus would be unable to cause much harm.  Such drugs are known as antiviral agents.

Are antiviral agents effective in other viral infections? Although many viral infections lack an effective drug to stop the virus multiplying, there are  also a large number of infections where antiviral drugs are useful.  These  drug names often end in ‘vir’.  Most widely known is acicolovir/acyclovir (trade name Zovirax), which can even be bought ‘over the counter’ for the treatment of cold sores and shingles. There are also a number of antiviral drugs that work in influenza.  These include drugs such as oseltamivir (known as Tamiflu) and zanamivir (known as Relenza).  Indeed, in the previous epidemics of bird flu and swine flu, governments spent millions stockpiling these drugs.  They were of variable benefit and in fact were never widely used. There are also now at least 20 antiviral agents that have been used to stop viral multiplication in HIV/AIDS.

Does each virus need its own antiviral drug? Antibiotics, such as  penicillin, are typically active against many different bacteria.  The range of bacteria covered by one antibiotic can vary. Some antibiotics are ‘narrow spectrum’ and active against a few bacteria , whereas some are ‘broad spectrum’ and active against a larger range.  By contrast there are very few antiviral drugs that are considered broad spectrum (apart from remdesivir, see below) and most are very specific.  Indeed, the large number of drugs used to treat the AIDS virus attack very different aspects of the virus’s activity (and indeed are used in combination).

Where to start looking for antiviral drug against Covid-19? One major hope was that there might be no need to develop a new antiviral drug, as that would take too long, but that drugs of known benefit in other viral illnesses could be also used for Covid-19.  Covid-19 is one of a family of so called RNA viruses which include those that caused the epidemics with SARS in 2002 and the MERS (Middle Eastern Respiratory Syndrome) in 2012.  It is also related to the Ebola virus which caused such concerns in Western Africa in 2014-16. 

Remdesivir is one of the few broad spectrum antiviral agents and has the potential to block the pathway by which RNA viruses multiply.  It was originally hoped it would be useful to combat the Ebola and MERS pandemics.  In practice, in clinical trials, remdesivir did not prove useful in treating Ebola but the drug was still a strong candidate to try in Covid-19. 

There have been at least 10 trials and there are now a number of studies suggesting that this drug can be useful in severe Covid-19.  The most widely published study showed that in patients who developed severe lung complications, remdesivir reduced the length of time  a patient was in hospital from an average of 15 to an average of 11 days.  Around 20% had serious side effects.  Thus, whilst useful it is not a miracle cure and the safety profile means that it is not suitable for widespread use in  people with mild disease.

Are there any new antiviral drugs on the horizon that can treat people with early Covid-19 to prevent serious complications?

As implied above most of the work has been done on reusing (or ‘repurposing’ in the jargon) existing drugs, and there is no obvious candidate.  To develop a drug from scratch that is directed towards Covid-19 will take some time.  The approach is first to study how the  virus divides and attacks human cells.  This information is then used to design drugs to block such actions.  This can be very complex work but in June research from California has achieved in 3 months what in normal times can take two years.  The research has identified the key mechanism that the virus uses to multiply in human cells and is now starting to design drugs to address this.  They will have to be tested carefully of course for safety and benefit.  Even with success at every stage, having a new drug available for widespread use must be a couple of years away.

Does resistance occur with antiviral drugs?

Like everything else the answer is ‘it varies’!  It depends on whether the virus mutates in such a way that is still causes illness but escapes the process by which the drug works.  The cold sore virus has not become resistant to acicolovir as far as I am aware, despite the drug being so widely available.  By contrast the problem for patients with HIV/AIDS is that the development of new antiviral agents barely keeps up with the development of resistance to existing agents. It is too early to know for sure whether Covid-19 virus will develop resistance to remdesivir but a study at the end of June, from India and Japan, suggests that the virus could mutate to become resistant to remdesivir.

One problem with Covid-19 is the long incubation period

The incubation period for seasonal flu is probably about two days.  Indeed, the studies with Tamiflu showed that one needed to take it within a day of symptoms appearing to have the desired effect.  Covid-19 has a longer incubation period of maybe 5-7 days and by the time that symptoms are present, the virus has already multiplied and it is perhaps too late for any antiviral drug to work.  However, recent research from Belgium using computer simulations has shown that with a robust ‘track and trace’ system which can identify individuals and their contacts with the virus, the use of antiviral drugs even before any symptoms appear can make a big difference in helping control local outbreaks


  • There are no existing drugs that are useful in treating people with Covid-19 to prevent the infection becoming serious.
  • It should be possible to develop new drugs to stop the virus multiplying  in the body’s cells and prevent the serious complications
  • This will take time to develop and especially to prove the drugs are safe and do not cause more health problems than they prevent
  • Being optimistic, strategies that combine successful contact tracing and testing with early use of any such treatments could be an alternative to a vaccine if the latter proves too difficult to achieve