Medicine against dengue is in the pre-clinical testing phase – 03/13/2024 – Health

Research into the development of antiviral drugs gained new momentum with the Covid pandemic. However, the cooling of urgency accompanied the reduction in investments. Now, researchers are betting on drugs that can treat more than one virus at the same time.

This is said by American scientist Jeffrey Glenn, professor of immunology and microbiology at Stanford University who leads research into the development of antivirals for arboviruses, which transmit dengue and chikungunya.

In Brazil this Wednesday (13) for a visit to Ciência Pioneira, an initiative to support science, the molecular virologist already has a history of participating in studies with Brazilians — he was part of the group that observed a medicine that was successful in reducing risks of hospitalization in cases of Covid-19.

Its new project to develop antivirals against arboviruses had good results in tests on cells, in the laboratory, and also in tolerability tests, and is expected to enter the animal testing phase in April, in a pre-clinical phase, in a likely partnership with UFMG (Federal University of Minas Gerais). The first results are expected to appear by the beginning of the second half of the year.

You have a track record in developing antivirals. How do antivirals act in the body, especially those developed against dengue?
Unfortunately, the number of antivirals available to combat the large number of threats that exist is relatively small and leaves many gaps in our collective antiviral defenses.

This type of medicine works against viruses in the same way that antibiotics work against bacterial infections. Antivirals seek to interfere with the virus’s life cycle and can help the immune system get rid of the infection.

For dengue, and in many other cases, there is also a risk of the virus mutating to become resistant to a particular antiviral. Thus, one approach is to try to develop a cocktail of several antiviral agents that could be used together to decrease the likelihood of the virus becoming resistant to treatment.

What are the challenges in this area of ​​research?
It takes a lot of effort to develop even a good dengue medicine, let alone a cocktail of antivirals. We are working on new drug candidates to be used alone or in combination with other antivirals against dengue.

Was there a change in investment by the public and private sectors in the development of antivirals after the pandemic?
Certainly, during the pandemic there was an increase in investments in the development of antivirals. This investment came from industry, government and philanthropy. Unfortunately, as the pandemic has subsided, so has the magnitude of these investments.

When it comes to developing antivirals for pandemics, it is important to act proactively, that is, before the next pandemic, not reactively, after millions of deaths. Drug development takes time, so it is very dangerous that we are not making enough investments in this area.

That said, for an antiviral to be useful in stopping a future pandemic, it needs to be fully developed and stockpiled in advance. This is very expensive and making this investment for a virus that may never appear is a huge challenge, regardless of whether it is funded by the government, non-profits or investors. Therefore, it is important that there is a good business case for the drug in non-pandemic times.

For example, a medicine developed to combat future influenza pandemics, which could kill hundreds of millions of people, could also be used to treat regular seasonal flu. Or a drug developed to treat Covid that could also be used to treat cancer. We are adopting a similar strategy in our efforts to find a solution to dengue.

What is the scientific scenario in antiviral research against dengue?
There are several possible approaches. In one of them, we can seek to develop medicines that target a specific element within the dengue virus, so-called direct-acting antivirals.

Secondly, we can seek to develop drugs that can deprive the virus of access to something the virus needs in us to grow, so-called antivirals that target the host.

Third, there is a new class of drugs we call “programmable antivirals” that we can quickly “program” or engineer against specific features in the dengue virus genome.

How has your research progressed in developing antivirals for arboviruses? Can you talk about the methodology and results obtained so far?
At Stanford, we have focused on developing new types of medicines since its inception with a strong emphasis on medicinal chemistry. This involves designing, synthesizing and testing new molecules.

Tests are usually done first on virus-infected cells grown in the laboratory, and the most promising compounds are then tested in infected animals. [A pesquisa é feita a partir do estudo de desenvolvimento de antivirais para hepatite e faz parte da abordagem de antivirais de ação direta, por agirem diretamente no vírus — são pequenas moléculas que se ligam a uma proteína do vírus, de forma a inibir a replicação vira].

It looks like we have some promising candidates and are continuing to optimize the top ones further. We are still in the pre-clinical testing phase.

I also believe that lambda interferon [peguilado, substância ainda sem autorização para uso comercial no Brasil, do estudo que pesquisa um medicamento para a Covid]which has broad-spectrum antiviral activity and has been administered to thousands of patients in multiple international trials, including here in Brazil, could be very good for many key arbovirus infections.

Can antivirals be a solution to an epidemic in the country? In conjunction with the vaccine, is it a good way to combat dengue?
Ideally, both antivirals and vaccines are effective. We need both. Vaccines try to prevent disease, and antivirals treat people who are already infected when it is too late for the vaccine to be of benefit.

Furthermore, to make a vaccine, you need to know what the target virus is. And some viruses are very difficult to make vaccines against. For example, even after decades of trying, we still do not have vaccines for hepatitis C or HIV.

Sometimes we get lucky, like with Covid, but even so, with the largest investment ever made, for Operation Warp Speed, [parceria público-privada iniciada pelos Estados Unidos para acelerar o desenvolvimento, a fabricação e a distribuição de vacinas e diagnósticos da Covid]it took billions of dollars and more than a year from the start of the pandemic to the shipment of vaccines.

If we had an effective antiviral on hand, we could have hope of controlling the pandemic in Wuhan. Because antivirals can often be broad-spectrum, they can be developed against specific viruses, but they have a chance of working against other viruses, even those we don’t yet know exist.

You were part of the group that researched an experimental medicine that reduced the risk of hospitalization in cases of Covid by half. Is there any news about this study or the prospect of commercializing the drug?
This was an effort made with a great team based here in Brazil that I was very proud to be part of.

In fact, the risk of hospitalization was reduced by half in patients who were already vaccinated. In unvaccinated patients treated early, there was an 89% reduction in hospitalizations and deaths. Furthermore, it was effective against all Covid variants, and the side effects were the same as the placebo.

Based on the available science, I believe that this treatment can be very effective against many other viruses, including some of those that have a major impact in Brazil.

Regarding commercialization, even if the phase 3 study of lambda for Covid is complete, lambda still needs to be approved by the regulatory authority of each individual country.