New Antibody Drugs Could Hit Crown to Treat or Prevent COVID-19: Study
Sun, April 11, 2021

New Antibody Drugs Could Hit Crown to Treat or Prevent COVID-19: Study


A new study showed that antibody drugs could treat and protect against COVID-19. Instead of interrupting the binding process, the drugs targeted the crown of spike proteins of the coronavirus.

The targeting of SARS-CoV-2's spike protein crown was demonstrated by scientists at the Agency for Science, Technology, and Research (A*STAR), a lead science institute in Singapore. Their breakthrough suggested blocking the crown of the spike proteins. This could stop the coronavirus from binding to healthy cells and prevent symptoms of COVID-19. The drugs were based on preconstructed antibodies to overcome the search for candidates. The novel approach showed promise in preclinical testing.

The Race on COVID-19 Vaccine

Hundreds of companies have joined the race on the first safe and effective COVID-19 vaccine. The majority of experimental vaccines are in early-stage clinical trials, while a handful reached late-stage studies. Many of these vaccines are using the messenger RNA of SARS-CoV-2 to induce an immune response. But others are utilizing different, innovative strategies to protect people from the coronavirus. Yet there is a lacking in the number of experimental vaccines specifically tailored for children and older adults.

According to Statista, a German portal for statistics, 142 experimental COVID-19 vaccines were in the preclinical stage, 29 in Phase 1 studies, 18 in Phase 2 studies, and nine in Phase 3 studies, as of September 8, 2020. One of the vaccines in Phase 3 is from the University of Oxford co-developed by AstraZeneca. Unfortunately, the clinical trials were paused due to a participant who developed a serious adverse event. Eventually, the Phase 3 studies resumed when the vaccine is confirmed safe. The Oxford COVID-19 vaccine is expected to finish the late-stage trials this year.

Meanwhile, the World Health Organization (WHO) of the United Nations reported 27,486,950 confirmed cases and 894,983 confirmed deaths due to COVID-19 worldwide, as of September 9, 2020. The WHO launched the COVID-19 Partners Platform on March 16, 2020. A total of 110 countries are using the platform to share their national COVID-19 response. While more than 142 nations are using it to support preparedness, response planning, and monitoring of the disease. But each country is desperately in need of a safe and effective vaccine to efficiently slow down community transmission and death rates.



Hitting the Crown of the Spike Protein

At A*STAR, scientists have achieved a breakthrough in therapeutic COVID-19 research. Their breakthrough suggests hitting the crown of the coronavirus' spike proteins. This strategy may treat and prevent COVID-19. To hit the crown, specific antibodies must be used. Once hit, the spike proteins are unlikely to bind to healthy cells and cause infection. Their method may be better compared to existing experimental vaccines or therapies.

"Our antibody discovery team consists of scientists specializing in antibody discovery and engineering. They have deep capabilities in these research areas, having worked on diseases such as chikungunya and dengue fever previously," said Wang Cheng-I, the lead investigator of the novel approach, which resulted in a partnership with a pharmaceutical company.

In the past six months, research on SARS-CoV-2 showed various details about its biology and structure. Researchers worldwide have discovered the mechanisms used by the coronavirus to infect. A*STAR scientists highlighted the crown or the halo of roughly 100 spike proteins of the coronavirus. The spike proteins are required by the pathogen to infect and hijack cells. Experimental vaccines are focused on these proteins to induce antibody activity. This is why some COVID-19 vaccines have mRNA to let cells produce the spike proteins, which the immune system will study and prepare for.



Certain therapies, on the other hand, are centered around the binding process. The primary objective is to treat COVID-19 and reduce symptoms. Most therapy designs involve disrupting the binding sequence, just like antibodies. But clinical efficacy of these therapies is considerably low. If the products reach the market, the effectiveness may even be lower.

The scientists discovered that attacking the crown is better than hitting the sequence itself. They looked into a large collection of diverse, pre-constructed antibodies to determine the best molecules for therapeutic purposes. This allowed them to mine for the potential candidates at a quicker and more efficient way, compared to searching from natural antibody sources. They applied an in vitro platform to test the pre-constructed antibodies.

Results revealed potential candidates for antibody drugs. Scientists singled out those with the highest attachment to the spike proteins. The candidates were also found capable of hindering the virus from interacting with host cell receptors. The antibodies could neutralize the coronavirus in experimental conditions. The neutralization reduced the viral replication in human airway epithelial cells by more than 10,000 times.

Wang explained that binding the crown stopped the virus from attacking healthy cells. The performance hinted at two applications of COVID-19 antibody drugs. First, the drugs could become prophylaxis to protect those in high-risk settings. And second, the drugs could be turned into vaccines for specific population groups, like people who are immunocompromised or children whose immune systems are yet to mature.

A third possible application would be treating patients with COVID-19. Since the antibodies could hit the crown, the coronavirus would lose its momentum and ability to replicate. This could increase the survivability of patients, raise their recovery rate, and avoid serious health complications, particularly inflammation and organ failure.

Despite the promising findings in lab settings, the approach is still in the infancy stage. Scientists have to study the safety profile of these experimental drugs. Introducing preconstructed antibodies may induce allergic reactions to some individuals. But the current state of the approach appears to be ready for early-stage clinical trials.



The A*STAR scientists have partnered with Japanese pharma Chugai Pharmabody Research. The partnership is now optimizing the antibody drugs for clinical application. As part of the optimization, they plan to use a type of engineering technology to adjust several aspects of the drugs. One of the adjustments includes the modification of antibody sequences or structures, which can improve efficacy and safety.