10 March 2020
COVID-19, the coronavirus that’s causing the current worldwide outbreak, invades cells by hijacking a protein on their surface called human receptor angiotensin-converting enzyme 2 (ACE2). Understanding the full structure of ACE2 could aid efforts to develop new detection and treatment techniques—and now a team of researchers from China is providing a map of the enzyme and the entry point it provides to COVID-19.
When COVID-19 infects a person, a “viral spike” or “S” protein binds to ACE2 on the surface of cells. ACE2 chaperones another protein called BOAT1, reported researchers led by Westlake University in Hangzhou in the journal Science. It was one of two coronavirus maps released last week that could inspire researchers who are searching for drugs and vaccines to combat the outbreak.
In describing the full-length structure of the ACE2-BOAT1 complex, the China-based researchers suggested several possible avenues to explore for potential treatments. For example, designing antibodies that target specific sites either on ACE2 or the S protein of the coronavirus could offer methods for suppressing the virus, they said. The role of BOAT1, which is mostly expressed in the kidneys and intestines, isn’t well understood, but further investigation could also inspire treatment ideas, they added.
“Our findings not only shed light on the mechanistic understanding of viral infection,” said the authors in a statement provided to Science, “but will also facilitate development of viral detection techniques and potential antiviral therapeutics.”
The similarities between COVID-19 and the coronavirus that caused the SARS outbreak of 2003 are inspiring other research teams to build upon discoveries made during that time in the hopes of finding solutions to the current outbreak. Early last week, for example, a team led by the University of Chicago reported that a protein shared by both viruses could be blocked to treat COVID-19.
The protein is called Nsp15. The researchers mapped the 3D structure of Nsp15 and published the map in an online database of proteins called RCSB.
Nsp15 in COVID-19 is about 89% identical to the protein from the 2003 SARS outbreak, the researchers said. The protein is known to play a role in the life cycle and virulence of coronaviruses. Recent studies suggest it helps the viruses replicate by blocking the immune response.
The new 3D map of Nsp15 will “shed light on the small, but potentially important differences between the two viruses that contribute to the different patterns in the spread and severity of the diseases they cause,” said co-author Adam Godzik, Ph.D., a professor of biomedical sciences at the University of California, Riverside School of Medicine, in a statement.
During the earlier SARS outbreak, drugs targeting Nsp15 were investigated, but none made it past early development because the epidemic ended. “The inhibitors that were developed for SARS now could be tested against this protein,” suggested co-author Karla Satchell, Ph.D., Northwestern professor and principal investigator for the Center for Structural Genomics of Infectious Diseases, in the statement.
The team is now planning to map the structure of additional COVID-19 proteins in the hopes of finding other potential drug targets.Print
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