Covid antiviral pills: What scientists still want to know

‘Drugs such as molnupiravir and Paxlovid could change the course of the pandemic if clinical trial results hold up in the real world...

‘Researchers will be looking at the ages and ethnicities of those who were enrolled in the trials, and at any other health conditions that they had, says John Mellors, an infectious-disease specialist at the University of Pittsburgh Medical Center in Pennsylvania.

‘Because antiviral drugs often need to be given early in the course of an infection for them to work effectively, Mellors will also be looking for more detail about when the drugs were given in the trials, and at how those timings correlated with efficacy. That information will provide a sense of when the window of opportunity for treatment closes. Neither trial had enough participants to enable firm conclusions to be drawn about the drugs’ ability to prevent deaths, but no deaths occurred in their treatment arms.

‘Researchers are also keen for any clue — including from further clinical trials — as to whether the drugs affect transmission of the coronavirus, or prevent illness in people who have been exposed to it.

‘If they do, the combination of vaccines and antiviral drugs could become a powerful tool in controlling outbreaks, says Jerome Kim, director-general of the International Vaccine Institute in Seoul. For example, if a worrying coronavirus variant emerges in a specific region, those who are most likely to be affected could be given an antiviral drug to supplement immunity from vaccines. This could clamp down on the virus and prevent its spread. “It opens up some new possibilities for the way we think about control,” Kim says. “This would have a really dramatic impact.”

Read here (Nature, Nov 10, 2021)

Merck’s antiviral could be just what Covid was waiting for

‘There's a possibility that SARS-CoV-2 could do an end run around the drug; any variant that happens to be less susceptible to the drug’s modus operandi could survive and become more dominant, pushing the virus’s evolution toward resistance. And SARS-CoV-2 has already shown its propensity for outsmarting certain treatments: In July 2021 the US halted shipments of an antibody therapy from Eli Lilly after detecting resistance in newer variants of the virus.’

Read here (Wired, Nov 1, 2021)

All about Molnupiravir, the anti-Covid pill

‘A new pill with the promise to treat Covid-19 is creating waves across the world and even at US$700 for a five-day course of treatment, it might just be a game changer. It is too early to tell if it will be available to Malaysians, although health minister Khairy Jamaluddin has revealed that he has started negotiations for Malaysia to procure the drug Molnupiravir, which is reputed to have shown a 50% reduction in the risk of hospitalisation and death.

‘Developed by US pharmaceutical giant Merck & Co, the pill has yet to get emergency authorisation by the US Food and Drug Administration (FDA). It would be the first Covid-19 oral antiviral medicine, if approved.

‘How does the pill work? The pill has been designed to introduce errors into the genetic code of the virus, thereby stopping effective replication. It is designed to be taken once someone displays Covid-19 symptoms. One course of the treatment lasts five days, with four capsules taken twice a day for a total of 40 pills.

‘How effective is it? Merck says the drug cuts the risk of hospitalisation or death in half according to trials conducted among 775 Covid-19 adults with mild-to-moderate Covid-19 symptoms. After 29 days, 7% of those who received the drug were hospitalised compared to 14% of those who received the placebo. No deaths were reported in patients who received Molnupiravir while there were eight deaths in patients who took the placebo, the company said.’

Read here (Free Malaysia Today, Oct 3, 2021)

There are few good Covid antivirals, but that could be changing

‘The COVID pandemic has now made new antiviral treatments a priority. But generating these therapies—especially direct-acting, orally administered drugs that inactivate viruses—is time-consuming. The reason monoclonal antibodies came along first is that scientists could simply follow the immune system’s lead and create synthetic versions of the natural antibodies that deflect the novel coronavirus, or SARS-CoV-2, from its host cell receptor in recovered patients. The goal of an antiviral pill is to stop the pathogen from replicating, but finding drugs that can do that without injuring the infected human cell is no easy task. Scientists start by screening thousands of compounds for their efficacy in targeting SARS-CoV-2 in cell culture. Promising candidates are then tested in animals—both to ensure that the drugs are not toxic and that they are not immediately destroyed in the body and reach tissues in the lungs and other organs in sufficient amounts. All this work takes place in high-level biosafety laboratories staffed by skilled workers, who are in short supply.’

Read here (Scientific American, July 15, 2021)

Oral drug effective against Covid in hamsters, now in final stages of human trials: Study

‘An orally-administered antiviral drug initially developed to treat influenza can significantly decrease novel coronavirus levels in hamsters and is in the final stages of human trials, holding out promise of a pill to combat COVID-19, say researchers.

‘Scientists from the National Institutes of Health (NIH) in the US and the University of Plymouth in the UK found that MK-4482, also called Molnupiravir, was effective when provided up to 12 hours before or 12 hours after infection with SARS-CoV-2, the novel coronavirus that causes COVID-19. The drug can also decrease damage it causes to lungs, states the study conducted on hamsters.

‘Published in the journal Nature Communications on April 16, it suggests that treatment with MK-4482 could potentially mitigate high-risk exposure to SARS-CoV-2 and might be used to treat established SARS-CoV-2 infection alone or in combination with other agents. There are currently no drugs suitable for high-risk exposure use against SARS-CoV-2, the researchers said.’

Read here (Economic Times, Times of India, Apr 19, 2021)

Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model

‘The COVID-19 pandemic progresses unabated in many regions of the world. An effective antiviral against SARS-CoV-2 that could be administered orally for use following high-risk exposure would be of substantial benefit in controlling the COVID-19 pandemic. Herein, we show that MK-4482, an orally administered nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model. The inhibitory effect of MK-4482 on SARS-CoV-2 replication is observed in animals when the drug is administered either beginning 12 h before or 12 h following infection in a high-risk exposure model. These data support the potential utility of MK-4482 to control SARS-CoV-2 infection in humans following high-risk exposure as well as for treatment of COVID-19 patients.’

Read here (Nature, Apr 16, 2021)

Molnupiravir: A new hope for prevention and treatment of Covid-19 and other dangerous viruses

‘The positive results of Molnupiravir represent an emerging hope for more Covid-19 therapies to come. Its oral administration indicates a potential drug that could come before hospitalization and perhaps even prevent severe symptoms. Were a pill-based treatment for Covid-19 available, many lives would be easily saved and many hospital beds could be opened for those who need them. 

‘In addition to its reduction of Covid-19 transmission, Molnupiravir is likely to be useful against influenza, ebola, and a large swath of other viruses as well. Its development appears to be a major advancement in virus control and should be active against Covid-19 variants and variants of other viruses. However, we caution Molnupiravir should be administered in conjunction with other therapies to avoid viruses rapidly developing resistance, which all these viruses are well-equipped to do. 

‘Though, as these results are preliminary, we eagerly await the full release of the phase two data and the drug’s eventual full trial outcomes. This could be a real winner.’

Read here (Forbes, Mar 16, 2021)

Oral Covid-19 treatment yields promising trial data: Drugmakers

‘German pharmaceutical giant Merck and a US partner reported promising results on Saturday (Mar 6) in trials of a drug administered orally to fight COVID-19, saying it helps reduce patients' viral load...

‘In January, Merck halted work on two COVID-19 vaccine candidates but has pressed on with research into two products to treat the disease, including a pill-based one called molnupiravir, which it has developed with Ridgeback Biotherapeutics.

‘This drug caused a significant drop in patients' viral load after five days of treatment with it, Merck said at a meeting with infectious disease experts. This Phase 2A test - drug trials have three stages before a product can be approved - was carried out among 202 non-hospitalised people with symptoms of COVID-19.’

Read here (Channel News Asia, Mar 7, 2021)