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For the past two years, the Covid-19 pandemic has taken over the world, so it is no surprise that scientists are studying this virus to understand how it works. Many researchers have been examining how the SARS-CoV-2 virus, which causes the disease COVID-19, infects human cells. To do this, researchers study how the virus interacts with proteins located on the surface of our cells that let them communicate with each other. Viruses like the SARS-CoV-2 virus attach to these receptors to enter a cell, where viruses can replicate.

It is known that SARS-CoV-2 uses a receptor called ACE2 which is found on a variety of cells, including the kidneys, liver, and lungs. However, scientists think it is very likely that there are also other receptors that SARS-CoV-2 uses to enter cells.

Scientists have considered whether a receptor known as HSPA5 could be another entry point that SARS-CoV-2 uses. Furthermore, in a study published in 2021, researchers speculated that the amount of a certain receptor protein, such as HSPA5 or ACE2, may determine which cells are affected by SARS-CoV-2. This is because large amounts of these receptors make cells more susceptible to SARS-CoV-2, since the virus has more places to enter.

Previous studies have shown that cancer patients are at a higher risk of exhibiting severe symptoms and death due to the SARS-CoV-2 virus. Aside from weakened immunity from cancer treatment, it is possible that COVID-19 patients with cancer may be more likely to have severe symptoms or die if their cancer cells have these receptors.  The scientists tested their hypothesis using information from online databases detailing the characteristics of COVID-19 infections and various cancers.

With this data, the researchers were able to measure the amount of ACE2 and HSPA5 receptors in normal cells to establish a baseline. Next, they studied the level of HSPA5 expressed in cancer patients to see if it is related to the patients’ survival. Last, they compared their receptor findings with available data regarding both the number and severity of malignant cancer patients that also had COVID-19 infections.

The researchers concluded that both normal and tumor tissues have HSPA5 receptors on their surface, but that tumor tissues have more HSPA5 than normal tissue. Cancers like colon adenocarcinoma and pancreatic adenocarcinoma, for example, have more HSPA5 receptors than ACE2 receptors. Additionally, the scientists found that malignant cancer patients more often developed severe COVID-19 when compared to all COVID-19 patients. While this may appear promising, this correlation was not investigated further, so it cannot definitively be concluded that this is related to the HSPA5 receptor.

Based on their findings, the researchers formed a new hypothesis –  when there are fewer ACE2 receptors, the SARS-CoV-2 virus will be more likely to invade cells with a lot of HSPA5. Essentially, when the doors are closed, the virus finds a window.

This data, while interesting, does not mean that cancers with more HSPA5 make patients more likely to die from COVID-19. They merely found that some cancers have more HSPA5, and that cancer patients have worse COVID-19 outcomes. Further testing would need to be done to test their new hypothesis. 

If further studies conclude that HSPA5 is a cell entry point for SARS-CoV-2, then targeting HSPA5 could be a way to prevent COVID-19 infections. This could be especially important for cancer patients as they are at higher risk for poor outcomes with COVID-19 infections and may have elevated levels of HSPA5. 

The authors cite some computer modeling studies that show that blocking the HSPA5 receptor could potentially interfere with COVID-19 infections, but it is not known if this would work in a living tissue or a patient. Regardless, studying HSPA5 could lead to new treatments for COVID-19 and aid in the prevention of severe cases which not only helps the patients but the healthcare system as a whole. 

Study Information

Original study: Evaluation and characterization of HSPA5 (GRP78) expression profiles in normal individuals and cancer patients with COVID-19

Study published on: 18 February 2021

Study author(s): Jiewen Fu, Chunli Wei, Jiayue He, Lianmei Zhang, Ju Zhou, Kyathegowdanadoddi Srinivasa Balaji, Shiyi Shen, Jiangzhou Peng, Amrish Sharma, and Junjiang Fu

The study was done at: Southwest Medical University (China), Nanjing Medical University (China), Southern Medical University (China), University of Mysore (India), The University of Texas (USA)

The study was funded by: National Natural Science Foundation of China, the Joint Research Foundation of Luzhou City and Southwest Medical University, and The Translational Medicine Foundation of Southwest Medical University

Raw data availability: Not Available

Featured image credit: Sciworthy