A new discovery in the ability of SARS-CoV-2 to infect cells may unlock better treatments. The coronavirus was found using heparan sulfate to bind and hijack healthy cells.
The discovery of heparan sulfate in SARS-CoV-2 was led by scientists at the University of California – San Diego (UCSD), a US public research university. The carbohydrate was found being used by the coronavirus to bind ACE2, the receptor required to infect healthy cells. If the carbohydrate was disrupted, the pathogen could no longer bind the receptor. The disruption would stop the coronavirus from attacking vulnerable cells in the upper respiratory tract. They published their findings in the journal Cell.
The Cases and Deaths Due to COVID-19 By Region
Millions of people have been infected with SARS-CoV-2 since the pandemic began. While hundreds of thousands of people died from COVID-19 worldwide. These cases and deaths happened due to the lack of specific treatment, cure, or vaccine for the novel disease. Unfortunately, experts do not expect a functional vaccine to become available this year. And if one is fully approved, it may not offer 100% protection and may require booster shots.
According to Statista, a German portal for statistics, as of September 13, 2020, 14,699,174 confirmed cases and 508,706 confirmed deaths were reported in the Region of the Americas. A total of 4,796,426 cases and 225,494 deaths were confirmed in the European Region. In Southeast Asia, 5,377,062 cases and 92,391 deaths were confirmed. In the Eastern Mediterranean Region, 2,101,676 cases and 55,012 deaths were reported. In Africa, 1,116,321 cases and 23,916 deaths were reported. And in the Western Pacific Region, 546,552 confirmed cases and 11,886 confirmed deaths were reported to the international community.
The global healthcare industry is fighting the pandemic on behalf of everyone. Unfortunately, many healthcare workers succumbed to the illness. As of September 3, 2020, Mexico had the highest confirmed deaths of healthcare workers due to COVID-19 at 1,320. It was followed by the US at 1,077, the UK at 649, Brazil at 634, Russia at 631, India at 573, South Africa at 240, and Italy at 188. These figures were obtained by Amnesty International.
The world needs a safe and effective vaccine to control COVID-19 transmission. This is one way to protect the healthcare system from collapsing.
The Carbohydrate Used by SARS-CoV-2 to Bind ACE2 Receptor
The research on SARS-CoV-2 showed that it needs to bind to the ACE2 receptor to infect healthy cells. This receptor can be found in almost every human cell. But the cells in the upper respiratory tract are preferred by the coronavirus. Several COVID-19 vaccines are designed using the spike protein of the virus. By exposing a person to the spike protein using a vector, the immune system can be armed with antibodies before the wild strain attacks. This can reduce the severity of symptoms and the risk of serious health complications.
At UCSD, scientists discovered something interesting in the binding process of the receptor. Their study showed a carbohydrate utilized by the coronavirus to bind the receptor. Without the carbohydrate, the coronavirus could not attach to the receptor and use it to hijack healthy cells. As such, their findings could significantly assist research on COVID-19 drugs. Any drug that could interfere with this carbohydrate might disable the pathogen's ability to infect.
"ACE2 is only part of the story. It isn't the whole picture," said Dr. Jeffrey Esko, a lead author of the study and co-director of the Glycobiology Research and Training Center at UCSD.
Dr. Thomas Mandel Clausen, also a study's lead author, found insight from another study that suggested an interaction between spike proteins and a carbohydrate, which was related to heparan sulfate. Dr. Daniel Sandoval, a postdoctoral researcher, also had the same thing in mind. Within a week, the entire team tested their theories in lab settings: a carbohydrate interacting with the spike proteins. They found the carbohydrate in question – heparan sulfate itself. They observed that the coronavirus used it to successfully infect cells.
They investigated further to learn the exact interactions. They used heparin, a commonly used medication for managing blood clots, to examine the interactions. The spike proteins were bound to heparin. The receptor-binding domain was opened and it increased the binding potential to the ACE2 receptor. During the cellular hijack, SARS-CoV-2 would bind both the carbohydrate on the cell's surface and ACE2.
After the discovery, they searched for methods that could disrupt the binding process. If they could disrupt it, SARS-CoV-2's ability to infect would be disabled. They found specific enzymes that could eliminate heparan sulfate from cell surfaces. That left the coronavirus without a critical resource to bind the receptor. The same effect was established using heparin.
The scientists modified heparin to remove the anticoagulant part designed to prevent blood clots. At the current doses given to patients, heparin treatment worked as an antiviral for SARS-CoV-2. However, the findings could not be translated yet into COVID-19 treatment. The findings were only observed in cells grown in labs. They have to test heparin and heparan sulfate inhibitors in animal models. If these substances could disrupt the carbohydrates, the team could develop a new drug and propose it for Phase 1 clinical trials.
Aside from that, another study led by UCSD scientists would explore the relationship of the gut microbiome with heparan sulfate. Microbes in the gut might alter the carbohydrate and in turn, might increase or decrease the susceptibility of a person to SARS-CoV-2. For now, the findings demonstrated two ways to remove the carbohydrates: using enzymes or bait and switch tools like heparin. Either of the two could reduce the ability of the coronavirus to infect cells by 80% to 90%.
The study findings add new insights into COVID-19. As mentioned, the therapeutic approach is yet to finish preclinical testing. No one suggested taking heparin as a preventative or treatment for the disease. If taken without medical guidance, heparin will increase the risk of bleeding and related complications, including heparin-induced thrombocytopenia. Though rare, severe allergic reactions to heparin have been documented before.