Neutralisation of SARS-CoV-2 by destruction of the prefusion Spike
Published:June 19, 2020DOI:https://doi.org/10.1016/j.chom.2020.06.010
Summary
There are as yet no licenced therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric Spike whose receptor binding domain (RBD) recognises angiotensin-converting enzyme 2 (ACE2), initiating conformational changes that drive membrane fusion. We find that the monoclonal antibody CR3022 binds the RBD tightly, neutralising SARS-CoV-2 and report the crystal structure at 2.4 Å of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilising, CR3022 epitope is inaccessible in the prefusion Spike, suggesting that CR3022 binding facilitates conversion to the fusion-incompetent post-fusion state. Cryo-EM analysis confirms that incubation of Spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope may be useful therapeutically, possibly in synergy with an antibody blocking receptor attachment.
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Article Info
Publication History
Accepted: June 12, 2020
Received in revised form: May 22, 2020
Received: May 13, 2020
Publication stage
In Press Accepted ManuscriptIdentification
Copyright
© 2020 Published by Elsevier Inc.
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Comments
GENTLE PEOPLE:
Scientists are discovering that infected asymptomatic people have a lower immune response than do symptomatic people. It makes sense because the SARS-CoV-2 has the ability to hide from the body's antiviral immune response and therefore the immune response does not sense the danger until it is almost too late. It correlates like a surprise attack during a war where the body is suddenly over-whelmed by the virus and then attempts to fight back only to cause more damage. When it finally discovers the danger the immune system creates a large counter-attack creating a dangerous response which does more harm than good. Too many infected cells are destroyed along with the virus. The virus has quietly infiltrated every cell in the lungs and the lungs are destroyed by the immune system in an attempt to kill the virus.
The Covid-19 virus is sneaky and because a person is asymptomatic does not mean he or she is not infected. If a person is infected and feels nothing, that may be because the virus is incubating and hiding from the immune system. We absolutely need early testing to discover who is infected and who is not infected. All infected people need a vaccine to help the body identify the virus and stimulate an early immune response that does no harm except to the virus. Some vaccines now in the works will not do damage to the human cell host.
Vaccines are now being created by several companies around the world and it will not be long before all Corona viruses will be eradicated from our lives.
Scientists are discovering that infected asymptomatic people have a lower immune response than do symptomatic people. It makes sense because the SARS-CoV-2 has the ability to hide from the body's antiviral immune response and therefore the immune response does not sense the danger until it is almost too late. It correlates like a surprise attack during a war where the body is suddenly over-whelmed by the virus and then attempts to fight back only to cause more damage. When it finally discovers the danger the immune system creates a large counter-attack creating a dangerous response which does more harm than good. Too many infected cells are destroyed along with the virus. The virus has quietly infiltrated every cell in the lungs and the lungs are destroyed by the immune system in an attempt to kill the virus.
The Covid-19 virus is sneaky and because a person is asymptomatic does not mean he or she is not infected. If a person is infected and feels nothing, that may be because the virus is incubating and hiding from the immune system. We absolutely need early testing to discover who is infected and who is not infected. All infected people need a vaccine to help the body identify the virus and stimulate an early immune response that does no harm except to the virus. Some vaccines now in the works will not do damage to the human cell host.
Vaccines are now being created by several companies around the world and it will not be long before all Corona viruses will be eradicated from our lives.
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