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)

How the rise of antivirals may change the course of the pandemic

‘Making them isn't easy. But new pills to treat COVID-19 are now showing promise at curbing illness and saving lives...

‘Unlike vaccines that can prevent infection, antivirals act as a second line of defense, slowing down and eventually arresting progression of a disease when infections occur. They’re also important when effective vaccines aren’t available against viral diseases, as is the case for HIV, hepatitis C, and herpes.

‘But developing antivirals is an expensive and difficult endeavor. That’s especially true for acute respiratory diseases, for which the window for treatment is short. In the case of SARS-CoV-2, the coronavirus that has unleashed the devastating COVID-19 pandemic, researchers have resorted to repurposing old drugs or compounds that were being tested against other diseases.’

Read here (National Geographic, Nov 5, 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)

Revealed: How a single pill home cure for Covid could be available this year

‘At two anonymous Pfizer buildings, one in the US and one in Belgium, a remarkable experiment is under way. Up to 60 volunteers, all clean-living adults aged between 18 and 60, are being given the first pill specifically designed to stop SARS-CoV-2.

‘If the trial is successful, it is just possible that a home cure for Covid-19 will become available later this year. The Prime Minister, who announced the formation of a UK Antivirals Taskforce last week specifically to invest in such products, will no doubt be scanning his text messages for early updates.

‘The molecule being tested is a bespoke antiviral codenamed PF 07321332. Classed as a "protease inhibitor", it has been formulated to attack the "spine" of the SARS-Cov-2 virus and stop it replicating in our noses, throats and lungs. It was protease inhibitors that turned the tide on the spread of HIV in the UK and around the world. Now researchers hope they may be on the brink of a similar pandemic-busting breakthrough.’

Read here (The Telegraph, Apr 24, 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)

The race for antiviral drugs to beat Covid — and the next pandemic

‘Despite dire warnings, a stockpile of ready compounds to fight viral pandemics was sorely lacking. Can drugmakers finally do the right thing?...

“What we will hopefully find”, he [Alejandro Chavez, a bioengineer and antiviral drug researcher at Columbia University Irving Medical Center in New York City] says, “are inhibitors that work on, if you’re really lucky, an entire family.” That would make the best-case scenario a pan-coronavirus inhibitor. But a more reasonable goal might be developing a drug for a subset of coronaviruses, such as alphacoronaviruses, which currently cause non-lethal infections in humans, and having a different drug for betacoronaviruses, the group responsible for SARS, MERS, and COVID-19.

‘Once the viral lineage is identified, “the same principles of drug discovery apply”, says Marnix Van Loock, head of emerging pathogens at Johnson & Johnson’s global public-health unit in Beerse, Belgium. As he explains, researchers need to find ‘druggable pockets’ on the surface of essential enzymes that are conserved between related viruses and can be used to design active molecules.’

Read here (Nature, Apr 14, 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)

Why it’s so hard to make antiviral drugs for Covid and other diseases

‘Antibiotics abound, but virus-fighting drugs are harder to come by. Fortunately, scientists are getting better at making and finding them...

‘The pandemic has sent scientists scrambling to find treatments. Heise [virologist Mark Heise of the University of North Carolina at Chapel Hill], for one, is testing a wide range of drugs—not just standard antivirals—against SARS-CoV-2 in lab dishes, as part of the Rapidly Emerging Antiviral Drug Discovery Initiative (READDI). The idea is that, because the virus depends on many processes in human cells, a variety of medications that act on human proteins might give doctors an edge by hurting the virus more than the patient. That throws the doors open to considering medications that were originally designed for cancer, psychosis, inflammatory conditions and autoimmune disease, to see if they might have a shot against Covid-19.

‘But the READDI collaborators—including academic centers, pharmaceutical companies and nongovernmental organizations—are aiming for more than a Covid-19 treatment. READDI hopes to identify and test potential medications for as-yet-unknown infections that may crop up in the future.

‘By getting early human safety testing done ahead of time, they’ll be ready to spring into action when those future outbreaks happen. As Heise says, “We don’t want to repeat what we’ve just been through.”

Read here (Scientific American, Feb 11, 2021)

These drugs might prevent severe Covid

‘Even with vaccines on the way, treatments are needed to prevent the disease from getting worse—and to be ready for COVID-25, COVID-37, and so on...

‘In an interview with Scientific American, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, described the desired characteristics of early COVID treatments. “My overwhelming preference is for direct-acting antiviral agents that can be administered orally” and that suppress the virus completely within a week or less, he said. “That, to me, is the highest priority.” 

‘Scientists have begun on differing paths to search for these drugs... One of the current leading contenders for treating mild COVID is an antiviral pill that was previously developed for influenza. At first called EIDD-2801, the drug was found to protect mice from severe lung disease caused by two other coronaviruses—SARS-CoV and MERS-CoV... 

‘Repurposing existing drugs can also yield some surprises by finding ones that are not logical candidates to work against COVID-19. Fluvoxamine, a pill used for treating anxiety disorders, shows some promise in treating early COVID...’

Read here (Scientific American, Dec 14, 2020) 

WHO study says remdesivir did not cut hospital stay or mortality in Covid-19 patients. Same with hydroxychloroquine, anti-HIV drug combination lopinavir/ritonavir and interferon

‘Gilead Sciences Inc's GILD.O remdesivir had little or no effect on COVID-19 patients' length of hospital stay or chances of survival, a clinical trial by the World Health Organization (WHO) has found. The antiviral medication, among the first to be used as a treatment for COVID-19, was one of the drugs recently used to treat U.S. President Donald Trump’s coronavirus infection.

‘The results are from WHO’s “Solidarity” trial, which evaluated the effects of four potential drug regimens, including remdesivir, hydroxychloroquine, anti-HIV drug combination lopinavir/ritonavir and interferon, in 11,266 adult patients across more than 30 countries. The study found the regimens appeared to have little or no effect on 28-day mortality or the length of the in-hospital course among patients hospitalized with COVID-19, the WHO said on Thursday.’

Read here (Reuters, Oct 16, 2020)

Lessons for Covid-19 from the early days of AIDS

‘Thirty-six years ago, we were, like today, in the midst of a new and still somewhat mysterious global pandemic. In the U.S. alone, more than one million people were infected with HIV, and 12,000 had already died of AIDS. At the time, we were just beginning to understand how the virus worked. But that didn’t stop some leaders from making wildly optimistic claims about an AIDS vaccine being delivered within two years.

‘Now, with COVID-19, we are in a remarkably similar spot: 2.7 million people have been infected across the U.S., and 128,000 have died of the disease. Despite our limited understanding of how the novel coronavirus works and what it does to the human body, many are putting what I consider a disproportionate amount of faith in the possibility of a COVID-19 vaccine by 2021. My feelings today echo my feelings a third of a century ago: yes, a vaccine may be possible, but it is by no means a certainty.’

Read here (Scientific American, July 6, 2020)

Famed HIV researcher on the race to find a Covid-19 treatment

‘David Ho is in a race against time to find a treatment for COVID-19. Fortunately it's the kind of race he's run before. Ho, the famed virologist and director and CEO of the Aaron Diamond AIDS research center at Columbia University, rose to prominence decades ago with his HIV research. Now he's working to develop a drug that can interrupt the coronavirus' ability to replicate, which, if successful, could lead to a treatment for COVID-19. His team is also studying antibody responses to the virus and is among dozens of labs racing to develop treatments.

‘The Jack Ma Foundation recently gave Ho and other researchers at Columbia University a $2.1 million grant to support their efforts to identify antiviral drugs and antibodies that can be used to fight the coronavirus.

‘Ho: My group is not so much working on a vaccine. We're trying to discover small-molecule drugs or develop antibodies that can be used either as prophylactics or therapeutics. We think the timeline for antibodies in particular can be much faster. We know we have the technology to fish out and construct very powerful antibodies that can be used to treat the infection, as well as prevent the infection.’

Read here (NBC News, May 1, 2020)