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An Unexpected Mode of Action for an Antibody

By February 4, 2019No Comments

Studies of human monoclonal antibodies isolated from survivors of coronavirus-induced severe acute respiratory syndrome (SARS) or Middle-East respiratory syndrome (MERS) are unveiling surprising immune defense tactics against fatal viruses. Atomic and molecular information about the workings of the highly potent antibodies may provide insights to prevent these serious and sometimes deadly lung infections.

Currently, no vaccines or specific treatments are available for any of the six coronaviruses that can infect humans.  Some of these coronaviruses cause only common-cold like symptoms, but others provoke lethal pneumonias. Past deadly outbreaks in several countries foreshadow the possibility of coronavirus-mediated pandemics. Additionally, genetic surveillance of coronaviruses in bats, and the fact that the MERS coronavirus naturally circulates in dromedary camels, suggest that  previous outbreaks may not be unusual incidences. The animal/human species barrier is likely to be crossed again and lead to new emerging coronaviruses in the future.

As part of anticipation and preparation initiatives, infectious disease research groups are trying to develop an anti-coronavirus arsenal. An international team headed by UW Medicine scientists is among those attempting to understand how SARS and MERS coronaviruses infect humans, and how their presence elicits a response from the immune system. The research group is particularly interested in how neutralizing antibodies target the coronavirus’ cell-invasion machinery.

Their most recent findings appear in the Jan. 31 online edition of Cell. The first authors are Alexandra Walls and Xiaoli Xiong, and the lead and senior author is David Veesler, all of the Department of Biochemistry at the University of Washington School of Medicine.

Coronaviruses have multifunctional surface spikes that recognize and attach to receptors on the surface of a host cell. They then fuse the virus and cellular membranes. They use these trimeric spike glycoproteins as their molecular break-in tool.