Scientists from the Experimental Drug Development Centre have discovered small molecules that target the Sars-CoV-2 virus' main protease.
PHOTO: ST ILLUSTRATION
Cheryl Tan
SINGAPORE - Local researchers here have a role to play in developing an important component of an antiviral drug to treat Covid-19.
Scientists from the Experimental Drug Development Centre (EDDC), a national platform hosted by the Agency for Science, Technology and Research (A*Star), have discovered small molecules that target the Sars-CoV-2 virus' main protease - a protein which is critical for the virus to replicate.
Professor Damian O'Connell, the chief executive of EDDC, told The Straits Times that the protease, known as the 3CL protease, is highly conserved across the different coronavirus mutations
The team has also proven through lab tests that the drug works against the Alpha, Beta, and Delta variants, as well as other known coronaviruses like Sars and Mers.
Asked if the drug will likely work against the Omicron variant as well, Prof O'Connell said it has not been tested but he would expect that the drug continues to remain effective.
EDDC had on Jan 14 announced a global licensing agreement with Chinese biotech firm Everest Medicines, giving the company the exclusive worldwide rights to develop, manufacture and commercialise EDDC's 3CL protease inhibitor - known as EDDC-2214 - as an oral antiviral therapy against Covid-19.
Dr Kerry Blanchard, chief executive of Everest Medicines, told ST that it is expected to start phase one trials by the end of the year, which will be among healthy volunteers to test for the drug's safety.
Asked about the patient profile that the drug will be targeting, Dr Blanchard said the company hopes to target "a wide range of patients", given its high efficacy shown in pre-clinical trial results.
He added that the drug will likely be available after next year, depending on the regulatory approval environment for the drug's emergency use authorisation.
EDDC-2214's targeting mechanism is similar to that of Pfizer's antiviral drug, paxlovid, which also targets the 3CL protease.
"From a global health perspective, it is important for us to have more than one drug even though they have the same mechanisms so that we can provide (more drugs) across multiple geographic regions," said Prof O'Connell.
"We've seen the emergence of multiple mRNA vaccines, how important they are, and how they've been utilised in a complementary way across the world, so it'll be very much the case here as well," he added.
Dr Shawn Vasoo, clinical director of the National Centre for Infectious Diseases, told ST that paxlovid, and another antiviral, molnupiravir, are currently being reviewed by the Health Sciences Authority (HSA).
Both drugs have already received approval by the United States' Food and Drug Administration (FDA), he noted.
Pfizer said that large-scale clinical trials have shown that the paxlovid drug was able to reduce hospitalisations or death by 89 per cent for those at risk of developing severe disease.
Likewise, trial results from molnupiravir have shown that the drug is able to halve the likelihood of dying or being hospitalised for those at risk of severe illness.
Dr Vasoo said that paxlovid, as with other Covid-19 specific treatments, may be considered for patients with risk factors for severe disease, such as those with poor immune systems or certain medical conditions.
"Vaccination is still the mainstay for prevention, and the vast majority (who are infected) will do well and not require any specific treatments if they do not have any risk factors for severe disease," he added.
Dr Vasoo also pointed out that not all Covid-19 treatments are suitable for specific patients, and doctors will have to evaluate their medical history to assess their suitability.
Current Covid-19 treatment drugs include:
Monoclonal antibodies for mild-to-moderate Covid-19
These are laboratory-made proteins that act like antibodies in helping the body to fight off infection.
It can be used to treat patients who do not require oxygen supplementation and have mild to moderate Covid-19 disease but are at risk of progressing to more serious illness.
Drugs include GlaxoSmithKline and Vir Biotechnology's sotrovimab and Regeneron and Roche's antibody cocktail REGN-COV2.
Singapore has also signed a supply and purchase agreement for AstraZeneca's antibody cocktail, Evusheld. However, it has yet to be approved by the Health Sciences Authority.
For severe Covid-19:
Antiviral remdesivir
When administered at the early stage of Covid-19 disease, remdesivir can help to hasten the time to recovery. It is usually used on patients who need low amounts of oxygen support.
Steroid dexamethasone and arthritis drugs tocilizumab and baricitinib
These drugs are typically used to reduce inflammation in patients with severe Covid-19, and can help to reduce death.
Cheryl Tan
SINGAPORE - Local researchers here have a role to play in developing an important component of an antiviral drug to treat Covid-19.
Scientists from the Experimental Drug Development Centre (EDDC), a national platform hosted by the Agency for Science, Technology and Research (A*Star), have discovered small molecules that target the Sars-CoV-2 virus' main protease - a protein which is critical for the virus to replicate.
Professor Damian O'Connell, the chief executive of EDDC, told The Straits Times that the protease, known as the 3CL protease, is highly conserved across the different coronavirus mutations
The team has also proven through lab tests that the drug works against the Alpha, Beta, and Delta variants, as well as other known coronaviruses like Sars and Mers.
Asked if the drug will likely work against the Omicron variant as well, Prof O'Connell said it has not been tested but he would expect that the drug continues to remain effective.
EDDC had on Jan 14 announced a global licensing agreement with Chinese biotech firm Everest Medicines, giving the company the exclusive worldwide rights to develop, manufacture and commercialise EDDC's 3CL protease inhibitor - known as EDDC-2214 - as an oral antiviral therapy against Covid-19.
Dr Kerry Blanchard, chief executive of Everest Medicines, told ST that it is expected to start phase one trials by the end of the year, which will be among healthy volunteers to test for the drug's safety.
Asked about the patient profile that the drug will be targeting, Dr Blanchard said the company hopes to target "a wide range of patients", given its high efficacy shown in pre-clinical trial results.
He added that the drug will likely be available after next year, depending on the regulatory approval environment for the drug's emergency use authorisation.
EDDC-2214's targeting mechanism is similar to that of Pfizer's antiviral drug, paxlovid, which also targets the 3CL protease.
"From a global health perspective, it is important for us to have more than one drug even though they have the same mechanisms so that we can provide (more drugs) across multiple geographic regions," said Prof O'Connell.
"We've seen the emergence of multiple mRNA vaccines, how important they are, and how they've been utilised in a complementary way across the world, so it'll be very much the case here as well," he added.
Dr Shawn Vasoo, clinical director of the National Centre for Infectious Diseases, told ST that paxlovid, and another antiviral, molnupiravir, are currently being reviewed by the Health Sciences Authority (HSA).
Both drugs have already received approval by the United States' Food and Drug Administration (FDA), he noted.
Pfizer said that large-scale clinical trials have shown that the paxlovid drug was able to reduce hospitalisations or death by 89 per cent for those at risk of developing severe disease.
Likewise, trial results from molnupiravir have shown that the drug is able to halve the likelihood of dying or being hospitalised for those at risk of severe illness.
Dr Vasoo said that paxlovid, as with other Covid-19 specific treatments, may be considered for patients with risk factors for severe disease, such as those with poor immune systems or certain medical conditions.
"Vaccination is still the mainstay for prevention, and the vast majority (who are infected) will do well and not require any specific treatments if they do not have any risk factors for severe disease," he added.
Dr Vasoo also pointed out that not all Covid-19 treatments are suitable for specific patients, and doctors will have to evaluate their medical history to assess their suitability.
Current Covid-19 treatment drugs include:
Monoclonal antibodies for mild-to-moderate Covid-19
These are laboratory-made proteins that act like antibodies in helping the body to fight off infection.
It can be used to treat patients who do not require oxygen supplementation and have mild to moderate Covid-19 disease but are at risk of progressing to more serious illness.
Drugs include GlaxoSmithKline and Vir Biotechnology's sotrovimab and Regeneron and Roche's antibody cocktail REGN-COV2.
Singapore has also signed a supply and purchase agreement for AstraZeneca's antibody cocktail, Evusheld. However, it has yet to be approved by the Health Sciences Authority.
For severe Covid-19:
Antiviral remdesivir
When administered at the early stage of Covid-19 disease, remdesivir can help to hasten the time to recovery. It is usually used on patients who need low amounts of oxygen support.
Steroid dexamethasone and arthritis drugs tocilizumab and baricitinib
These drugs are typically used to reduce inflammation in patients with severe Covid-19, and can help to reduce death.
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