Promising treatment for coronavirus

Since the advent of the new coronavirus in late 2019, multiple approaches have been considered to treat COVID-19. From the use of diversions such as the antimalaria drug hydroxychloroquine to the Ebola antiviral drug remdesivir.

Many of these treatment strategies are inadequate in terms of their clinical efficacy, and scientists are pushing to devise more targeted medicines to assist patients with COVID-19.

In a desperate race to find a way to stop this little killer, a team of researchers at A * STAR’s Singapore Immunology Network (SIgN), led by senior principal investigator Wanchen I, has found that SARS-inhibiting antibodies Significant progress has been made in identification-preventing the CoV-2 virus from invading human cells and blocking the symptoms of COVID-19.

The team recently established a partnership with Japanese pharmaceutical company Chugai Pharmabody Research and is currently working hard to bring these antibody candidates to the clinic.

Targeting viral crowns

A wealth of information on its structure and biology over the last 6 months Corona virus It was discovered. Named after the “crown” (approximately 100 halos of sugar-coated protein protrusions on the surface of the virus called spike proteins). SARS-CoV-2 uses these spike proteins to bind to receptors on human cells and allow entry. Infect will start.

Treatments tuned to disrupt this binding sequence are believed to be the best way to prevent the virus from harming its host, and antibodies are the natural answer to do just that. is. These Y-shaped proteins Immune cells Depending on the foreign intruder, it will not be able to latch a specific location of the virus and cause havoc to the lungs and other organs.

Over the last two decades, the evolution of sophisticated technology has led drug developers to take advantage of the exquisite target-binding properties of antibodies to transform them into safe and reliable therapies. There are already over 80 approved antibody drugs on the market. This includes several blockbusters for the treatment of cancer and inflammatory conditions.

Mining of antibody candidate drugs

The innate immune system is a rich source of antibody-producing cells that protect us from environmental hazards. This immune environment is incredibly vast and complex. It is estimated that humans make about 10 billion different antibodies, each capable of binding to specific antigens on the causative agent of the disease.

The challenge in COVID-19 drug development is to traverse this huge immune world and find a small number of antibodies that are strongly trapped in the SARS-CoV-2 spike protein. Even if they succeed in identifying these antibodies, only a very small subset of these have the biophysical properties required for an effective drug.

To solve the COVID-19 antibody puzzle, Wang et al. Used a discovery method that included “mining” of potential read candidates from a library of synthetic human antibodies. Instead of searching for naturally occurring antibody sources, the team explores a large collection of diverse pre-built antibodies and provides an advanced means of quickly finding specific molecules for therapeutic application. Did.

“Our antibody discovery team is made up of scientists who specialize in antibody discovery and engineering. They have deep abilities in these areas of research, previously for diseases such as chikungunya and dengue. We have been working on antibody candidate drugs. Wang is currently responsible for SIgN’s human monoclonal antibody technology platform.

Bench to bedside race

Using an in vitro antibody discovery platform, Wang’s team succeeded in selecting antibody molecules that bind strongly to the SARS-CoV-2 spike protein and prevent the virus from interacting with host cell receptors. .. In another big win, they have these antibody Can effectively neutralize live SARS-CoV-2 under conditions and reduce viral replication in human airway epithelial cells by a factor of 10,000. This is a functional characteristic that these clinical candidates are ready to treat.

“Antibodies bind to the crown to prevent the virus from adhering. Human cellsWang explained. This antibody has twice the potential for prevention and treatment. Prophylactic or prophylactic use of antibodies can provide temporary protection to healthcare professionals and those at high risk of infection, such as infections. Wang added that family antibodies from infected patients’ families, or those who are already sick, immunocompromised, elderly or young children who cannot use the COVID-19 vaccine, can also be used to treat infected patients. It was. “We believe that neutralizing antibody treatment slows virus replication, helps clear the virus from infected patients, and gives patients a good chance of fighting the disease,” he said.

A collaborative research collaboration between Wang’s group and Chugai’s Singapore-based research center was established in May 2020 with the aim of expediting this experiment. medicine To the clinic. To date, A * STAR and Chugai already have a fruitful history of collaboration, including the Global Health Innovative Technology Fund initiative to develop antibody countermeasures against other threats to global health such as dengue fever. ..

In this partnership, Chugai has promised to leverage its unique antibody engineering technology to further optimize the lead panels selected by the King’s team. This engineering process involves modifying antibody sequences or structures to enhance clinical functions such as enhancing their efficacy, improving their safety profile or prolonging their circulating half-life in humans.

“The outbreak of the new coronavirus is the most devastating threat faced by people around the world in decades,” said Osamu Okuda, president and chief operating officer of Chugai. “We hope that Chugai will work with A * STAR in a global effort to help address this threat and we will work together to open up clinical potential as soon as possible.”