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Credit: Megan Murrell / University of Minnesota
SARS-CoV-2, the virus that causes COVID-19It is highly infectious. Interestingly, in many patients, it triggers poor immune responses, which prolongs the disease. This helps the virus to spread widely, exacerbating the global pandemic. In a new study published in the procedures of the National Academy of SciencesResearchers at the University of Minnesota have identified the biochemical mechanism that can explain how the virus infects people efficiently while evading their immune responses.
This study, led by Fang Li, a professor at the College of Veterinary Medicine, examined the mechanism by which SARS-CoV-2 enters cells. Specifically, the team of scientists investigated how the virus “unblocks” human cells using a surface peak protein as the “key.” They made three important findings:
- the tip of the viral key binds tightly to human cells;
- the tip of the viral key is often hidden; and
- When new virus particles are created, the viral key is already pre-activated by a human enzyme.
“Usually, when a virus develops mechanisms to evade immune responses, it loses its potency to infect people,” Li said. However, SARS-CoV-2 maintains its infectivity using two mechanisms. First, during its limited exposure time, the tip of the viral key captures a receptor protein in human cells quickly and firmly. Second, preactivation of the viral key allows the virus to more effectively infect human cells. “
Li says that recognizing the avoidance of SARS-CoV-2 is important in designing antibody vaccines and drugs. Antibody drugs would need to dominate the tip of the hidden viral key by latching on very quickly and tightly during their limited exposure time. Alternatively, the drugs can target other parts of the viral key that are more exposed.
Li recommends that successful antiviral strategies should consider both the potency of the virus and its evasion.
Reference: “SARS-CoV-2 Cellular Entry Mechanisms” by Jian Shang, Yushun Wan, Chuming Luo, Gang Ye, Qibin Geng, Ashley Auerbach, and Fang Li, May 6, 2020, procedures of the National Academy of Sciences.
DOI: 10.1073 / pnas.2003138117
The study is co-authored by postdoctoral researchers Jian Shang, Yushun Wan, and Chuming Luo, graduate students Gang Ye and Qibin Geng, and junior scientist Ashley Auerbach. The National Institutes of Health funded the study.
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