Furthermore, they want to fully eliminate infectious diseases with the Next Pandemic
We would have coronaviruses unless we are tested for coronaviruses and then fired into space, leaving all other species and nature behind.” Dr. Benjamin Neuman, chief virologist at Texas A&M University’s Global Health Research Complex, agrees. Neuman has extensive experience with coronaviruses, having worked with them for decades. His experience won him a spot on the international committee that called the virus that causes Covid-19, SARS-CoV-2. SARS-CoV-2 is the newest member of the coronavirus family, which contains the viruses responsible for the SARS and MERS outbreaks.
The potential threat of coronaviruses or possible Next is increasing as the world’s climate changes and population grows, a threat that Neuman does not dismiss. He believes that certain viruses are very easy. Coronaviruses are on the other end of the continuum. “These are viruses that can creep around a cell and cut the wires before any warning bells go off.” Coronaviruses can be present in a wide variety of species, including bats, pangolins, and humans, he says.
A cunning opponent
SARS-CoV-2 has been able to live the high life for the past year, spreading undetected from one continent to the next and from one person to the next. Aside from the severe illness and death it may (and has) cause, this virus’s wanderlust has given it more opportunities to mutate, raising fears that vaccines, which have been produced at breakneck pace and are still successful against current variants, may no longer protect us.
Scientists are scrambling to find out how each new variant of SARS-CoV-2 differs from the previous one, and whether current vaccinations will avoid it. Many scientists, like Neuman, are taking a step back and seeing the bigger picture of coronaviruses, which isn’t limited to SARS-CoV-2 or a Covid-19 vaccine.
He states, “I like generalizable solutions.” “Knowing how to kill any coronavirus is important to me because science is this pursuit of generalizable knowledge.” He is sure that there are ways to do this.
SARS-CoV-2 isn’t the only coronavirus that can be killed
Neuman’s latest research focuses on antivirals, which are medicines that destroy or prevent viruses from replicating. Vaccines teach your immune system to destroy viruses, while antivirals teach your immune system to kill viruses. Antivirals have so far been largely ineffective against SARS-CoV-2 and are notoriously difficult to produce, in part due to the fact that viruses aren’t alive. Viruses, like the mythological undead, infiltrate our cells and use our bodies to carry out their will, making it difficult to eradicate them without also killing our cells.
Neuman claims that continuing to explore antivirals holds tremendous promise, but only if the current strategy, which has largely centered on creating antivirals that target parts of the virus that are likely to mutate, is seriously reconsidered.
According to Neuman, “some sections of the virus can shift over the course of an outbreak, or even over the course of a single infection.” These modifications have the potential to make a drug ineffective. “If you use drugs to attack such minor shifts, you easily end up with a resistant variant.” Mutations are appearing in the spike proteins of SARS-CoV-2, which stick out from the virus’s surface and give it a crownlike halo. The spike is the part of the virus that has ignited a lot of research into antivirals and vaccines.
While these vaccines and antivirals may be powerful enough to get us out of the current pandemic, they may be too unique to SARS-CoV-2 to be effective against a potential coronavirus. As a result, Neuman suggests that we should concentrate on parts of the virus that are less likely to mutate.
We don’t know if potential sinister viruses can be as easily addressed as SARS-CoV-2, so this isn’t just a case of “creating this mRNA capability and then going home.”
The linchpins that keep SARS-CoV-2 together are being targeted
“A strong antiviral can bind to one of the virus’s most basic components, such as an enzyme,” says Neuman. Even if those parts change, he believes, the virus will have a hard time replicating, making disease progression impossible. “You’re targeting the linchpins that are keeping all of these pieces of the virus together,” Neuman states, “and that’s going to be useful today and tomorrow.” Neuman’s collaborators are working on drugs that block these important enzymes. Neuman and his team aim to incorporate these inhibitors into cells in a dish if they are active in a test tube setting. If some of the inhibitors prove to be effective, researchers will test them against a variety of coronaviruses obtained from Covid-19 patients as well as the natural environment, including local sewers.
Neuman and his colleagues want to know not only whether these drugs work against a variety of coronavirus strains, but also at what point in the virus’s replication cycle they have an impact. This awareness is important when determining when to prescribe the drug to a patient. Consider what we heard from remdesivir: timing is all.
The repurposed Ebola medication was a hotly anticipated early Covid-19 treatment contender. Remdesivir was created to prevent many viruses, including SARS-CoV-2, from replicating their RNA, but evidence on its efficacy comes from patients who were already hospitalized when the virus multiplied and spread enough to cause Covid-19.
“If you start the therapy too late, it won’t work,” Neuman says. When a patient walks into a hospital, their immune system is already on high alert. The goal at that stage is to reduce the patient’s immune response so that their lungs do not fill with fluid. He explains that in order for remdesivir to be truly safe, it must be administered much earlier — long before a patient requires hospitalization. It’s possible that remdesivir is more successful than current research indicates, but Neuman assumes that combining it with other therapies would improve the probability of success.
SARS-CoV-2 is being ganged up
Antivirals have been shown to be most effective when used in conjunction with other antivirals. “Antivirals have the potential to gang up on a virus in ways that other therapeutics can’t,” Neuman says. It’s the HIV-fighting technique. Three medications are commonly used, each of which “pins down” a different part of the virus. He describes the end result as “brutally successful.”
The possibility of SARS-CoV-2 mutations evading current vaccines seems to be on everyone’s mind right now. Antivirals, according to Neuman, are a way of protecting lives by buying the immune system time if anything occurs that is resistant to vaccines, whether it’s a SARS-CoV-2 type or a new coronavirus entirely. “Antivirals have a role to play,” he states, “in complementing and assisting vaccines and other types of therapeutics.” Antivirals are there to place the virus in a headlock while the immune system takes care of the rest.”
In the case of vaccines, Neuman believes that mRNA vaccines are currently one of humanity’s most valuable properties. mRNA vaccines, in contrast to conventional protein-based vaccines (which include whooping cough, HPV, hepatitis B, and others), place the cells in charge of producing certain proteins, making it easier to change and scale up development.
The potential of mRNA vaccines to “turn on a dime” in the event of a viral mutation, as Michael Farzan, PhD, puts it, makes them an important weapon in the arsenal against coronaviruses. Farzan, chair of the Scripps Research Institute’s department of immunology and microbiology, believes their potential is limitless. ”We’ll be playing whack-a-mole with these viruses for a while, and we’ll need to be able to change vaccines to counteract them.” Farzan believes that with a more comprehensive approach to antivirals and vaccines, there will be no infectious disease in the not-too-distant future.
Getting choices is part of pandemic preparedness
Farzan and his colleagues were the first to discover ACE2 as a receptor for the original SARS strain, SARS-CoV, in 2003. SARS-CoV — and, it turns out, SARS-COV-2 — gain entry to our cells through ACE2, a protein on our cells. He smiles, “I get bragging rights on that one.” “For decades, no one cared, but now it’s relevant again.”
Despite the fact that Farzan is a fan of mRNA vaccines, he cautions against expecting too much from them. Scientists are also trying to figure out how mRNA vaccines affect our immune systems differently from other vaccines. Even if the vaccine we got is successful against all SARS-CoV-2 variants, we don’t know how long our post-vaccination immunity will last.
We don’t know if potential sinister viruses can be as easily handled as SARS-CoV-2, but he says it’s not just a matter of “creating this mRNA capability and then going home.” “We need to figure out what the limitations and strengths of using mRNA as a vaccine strategy are,” says Farzan. And, as we’re doing so, we’ll need a variety of tools. He says, “We need backups, we need options.”
Farzan and his team are working on a vaccine that targets the SARS-CoV-2 spike protein’s receptor-binding domain (RBD), which is far less likely to mutate than other parts of the spike. This is the same field that the Pfizer-BioNTech BNT162b2 vaccine targets. The difference is that Farzan and his colleagues want to make the RBD especially immunogenic, or engineered to elicit a stronger, longer-lasting immune response.
They’re adding another egg to the coronavirus vaccine basket by developing a protein-based version that’s safe enough to ship in powder form and then hydrate upon delivery, despite their desire to integrate their findings into an mRNA vaccine design. While this vaccine would lack the flexibility of an mRNA vaccine, it would avoid the extreme cold temperatures needed to ship and store an mRNA vaccine, which has been a problem during this pandemic. “It would be wonderful to be able to fully escape the cold chain issue,” Farzan says.
Beyond the one-bug-one-drug model
Farzan, like Neuman, sees antivirals as a critical component of pandemic preparedness. He says, “We need to step beyond one bug, one drug.”
He believes it is shortsighted to produce an antiviral that is unique to SARS-CoV-2. “But we also don’t want to try to make a medicine that works against every virus,” he warns. “The most powerful antivirals can eradicate a virus class.” Coronaviruses, for example, but even influenza viruses, Ebola viruses, and other infectious diseases may fall into this category. Farzan believes that with a more comprehensive approach to antivirals and vaccines, there will be no infectious disease in the not-too-distant future.
“Right now, infectious diseases are the lowest hanging fruit — they’re easier to deal with than cancer, heart disease, or neurodegenerative diseases,” he says. Farzan claims that, in addition to all of the other factors that destroy people, we have the tools to eradicate infectious diseases. He exclaims, “There is no modern technology that needs to be developed to make this possible.” “We are at a once-in-a-lifetime opportunity to develop technology that can grow faster than a virus.”
Farzan is adamant that the science to avoid the next pandemic already exists, but he reflects on the 20-year stretch in which he researched the SARS coronavirus before returning to his lab’s key research subject — HIV. He remembers the researchers who had come forward to study the coronavirus being quickly disbanded. He claims that there was no sustained effort. “We were all on to the next thing, and the last one had already passed us by.” He hopes it will not be the case with SARS-CoV-2, and that scientists will continue to collaborate and discuss their results freely.
Even if they do, Farzan has learned the hard way that research and scientists will not be enough to save us from the next pandemic. “It’s almost to the point that scientists aren’t as important as process control,” he says. As we step forward, he believes that providing integrated national and foreign facilities for rapidly scaling up a pandemic response — which would involve producing and delivering a vaccine or antiviral — is critical.