Antibody Points to Possible Weak Spot on Novel Coronavirus
Posted on by Dr. Francis Collins
Researchers are working hard to produce precise, 3D molecular maps to guide the development of safe, effective ways of combating the coronavirus disease 2019 (COVID-19) pandemic. While there’s been a lot of excitement surrounding the promise of antibody-based tests and treatments, this map you see above highlights another important use of antibodies: to inform efforts to design a vaccine.
This image shows the crystal structure of a human antibody (heavy chain in orange, light chain in yellow), which is a blood protein our immune systems produce to attack viruses and other foreign invaders. This particular antibody, called CR3022, is bound to a key surface protein of the novel coronavirus (white).
The CR3022 antibody actually doesn’t come from someone who has recovered from COVID-19. Instead, it was obtained from a person who, nearly two decades ago, survived a bout of severe acute respiratory syndrome (SARS). The SARS virus, which disappeared in 2004 after a brief outbreak in humans, is closely related to the novel coronavirus that causes COVID-19.
In a recent paper in the journal Science, the NIH-funded lab of Ian Wilson, The Scripps Research Institute, La Jolla, CA, along with colleagues at The University of Hong Kong, sought to understand how the human immune system interacts with and neutralizes this highly infectious virus [1]. The lab did so by employing high-resolution X-ray crystallography tools [2]. They captured the atomic structure of this antibody bound to its target by shooting X-rays through its crystallized form. (An antibody measures about 10 nanometers; a nanometer is 1 billionth of a meter.)
Other researchers had shown previously that CR3022 cross-reacts with the novel coronavirus, although the antibody doesn’t bind tightly enough to neutralize and stop it from infecting cells. So, Wilson’s team went to work to learn precisely where the antibody attaches to the novel virus. Those sites are of special interest because they highlight spots on a virus that are vulnerable to attack—and, as such, potentially good targets for vaccine designers.
A key finding in the new paper is that the antibody binds a highly similar site on both the SARS and novel coronaviruses. Those sites differ in each virus by just four amino acids, the building blocks of a protein.
This is particularly interesting because the antibody pictured above is bound to a spike protein, which is the appendage on both the SARS and novel coronavirus that enables them to bind to a key receptor protein on the surface of human cells, called ACE2. This binding activity marks the first step for these viruses in gaining entry into human cells and infecting them.
The human antibody shown in this image locks onto the virus’s spike protein at a different location than where the human ACE2 protein binds to the novel coronavirus. Intriguingly, the antibody binds to a spot on the novel coronavirus that is usually hidden, except for when virus shapeshifts its structure in order to infect a cell.
The findings suggest that a successful vaccine may be one that elicits antibodies that targets this same spot, but binds more tightly than the one seen above, thereby protecting human cells against the virus that causes COVID-19. However, Wilson notes that this study has just uncovered one potential vulnerability of the novel coronavirus, and it is likely the virus likely has many more that could be revealed with further study.
To continue in this quest to design a safe and effective vaccine, Wilson and his colleagues are now gathering blood samples to collect antibodies from people who’ve recovered from COVID-19. So, we can look forward to seeing some even more revealing images soon.
References:
[1] A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV. Yuan M, Wu NC, Zhu X, Lee CD, So RTY, Lv H, Mok CKP, Wilson IA. Science. 2020 Apr 3.
[2] 100 Years Later: Celebrating the Contributions of X-ray Crystallography to Allergy and Clinical Immunology. Pomés A, Chruszcz M, Gustchina A, Minor W, Mueller GA, Pedersen LC, Wlodawer A, Chapman MD. J Allergy Clin Immunol. 2015 Jul;136(1):29-37.
Links:
Coronaviruses (National Institute of Allergy and Infectious Diseases/NIH)
Coronavirus (COVID-19) (NIH)
Ian Wilson (The Scripps Research Institute, La Jolla, CA)
NIH Support: National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Institute of General Medical Sciences
You are studying Conception NOT infection!! Your perception is restricted to that of man. This is how God changes things on earth. Immunity will be attained by the next generation genetically from their “infected” parents. You might delay 100% but you can not prevent 100%in our future.
Excellent approach and worthy navigation. Thanks
lol.. God, by God you mean Wuhan Lab? Because my God is watching this shaking his head
Is it necessary really, these convolutions of complacent impressionablility expressed in the first and third commentary in this subordinate thread? The argument that this mainly seems to raise is that it would not seem unreasonable for the commentary function to be disabled!
Excellent. Science has become very expensive in the last 5 or 6 decades. It is important to display how there is no adequate substitute for science in hard times. It is not a question of how much it is expensive, it is a matter of have or have not.
worst pandemic ever for me 30 days at home until now
Thank You and continue using science based evidence and technology to combat covid-19.
Thank you for all information posted here, and for all your ongoing efforts to keep Americans healthy and safe! In connection with COVID-19, I keep wondering if a combination of an NSAID with anti-inflammatory activity (not acetaminophen) and an antihistamine started early at mild symptoms onset (fever, aches and upper respiratory symptoms) could prevent severe damage of the lungs developing later as a result of excessive inflammation. Existing NSAIDs and antihistamine drugs have been approved and used in various OTC combinations for treatment of symptoms associated with common cold and allergies. It seems to be a critical window of opportunity, a few days between the onset of mild symptoms and development of severe disease that requires hospitalization. The lung damage that causes a severe disease seems to be developing during these few days due to unfolding excessive inflammatory response of the body’s own immune system. An advantage of early anti-inflammatory intervention is that it would aim at prevention of complicated cases, and that OTC NSAID s are generally safer than chroloquine or related drugs and could be self-administered by many patients staying home with early mild symptoms (if approved by their medical providers). Thank you and God Bless!
Or . . .NIH could create healthy resistance and safe recovery for the entire population by promoting nutrient therapies that practitioners around the world are using to protect and recover patients. Vitamin C is at the top of the list, along with Vitamin D, A, zinc, and the precursors to glutathione. These along with oxygen therapies can address every single contagious infection, new and old. As wonderful as science can be, pursuit of pharmaceutical solutions must NOT mislead how discoveries are used. Vitamin C and other nutrients are the safe, effective, inexpensive, natural solutions and it is criminal they are not being embraced and disseminated now. Host susceptibility, not the properties of trillions of viruses on the planet, is what makes the difference between health and illness. NIH — please — redirect resources away from the highly profitable game of targeting each and every microbe with a unique drug or vaccine and enter the real world of healing by reducing host susceptibility.
Anecdotal information indicates very healthy young people still contract this virus, and some have died. Host susceptibility seems to follow when populations have not previously been exposed to a new, novel disease agent. Your suggestions could be useful adjuncts – but probably not the main agents of treatment.
But that’s something you can do yourself, Bernadette, isn’t it? Ensure your own adequate intake of such vitamins. That may lead you to have a stronger immune system, which — if you’ve been keeping up with the coronavirus discoveries — could actually result in a more severe infection and complicated symptoms. These nuances are why we need to investigate every contagion; because they are not all alike and often require unique treatments …
Thank you, Dr. Collins! This is excellent progress and news!
Quite an intriguing finding. Many thanks for the information
I have researched ACE2 and ACE as part of RAS for some time. I am retired in education, and out of work as offices and classrooms are closed. It is interesting that treating older patients many whom have CHF and or high BP with ACE inhibitors like lisinipril may actually act as a antagonist that increases the expression of ACE 2 and thus an entry point or vehicle into cell from viral transport.
Reduce availability of ACE2 activity and this may account in part for why women have less virulent or exposed to the viral actions. They may be carriers more than showing symptoms and younger people have less developed ACE2 receptors..
How can I provide blood samples for antibody examinations?
Dr Collins, Regarding the comment submitted by Philip Rotman (April 14) about ACE2 and Lisinipril, I would implore you to provide the best knowledge that NIH scientists could provide as there are many folks who take ACE2 inhibitors that might be at undue risk. Please look into this and reply with NIH’s best advice based on the best science available. With great appreciation for NIH and your leadership.
20 years of antibody immunity to SARS? Given this blog’s comparison of close similarity, what is a reasonable period of immunity conveyed to a SARS survivor, as a possible baseline assumption for SC2?This is a possibly key data point for modelling and prediction in the use of convalescent options, with implications for further mitigation models.
Re: comments by Philip Rotman and Robert Rager: The issue of hypertension, ACE inhibitors, angiotensin receptor blockers, and COVID-19 is way more complicated than you make it seem. I would urge you to read the latest information on this topic…
https://www.nejm.org/doi/full/10.1056/NEJMsr2005760
That is a very interesting find! Thank you so much for sharing 🙂
inhibit ace2 with angiotensin 2, and potassium sparing diuretics? tried to become a pharmacy tech, just failed. aseptic. former kidney patient.
thanks for the information
Thank you for sharing this information, I enjoyed this article.
Thank you for the information. Lately I’ve been trying to follow as much information available on the internet as possible. It’s new so there’s are confusions about the solutions or keeping the virus at bay. However I came across a nice video by WHO about the basics such as how to wash hands properly to wash away any aggressive foreign element on the skin. I hope someone finds the solution soon
Benadryl and advil?
Welp that’s it for me. I’m done sanitizing, cloroxing and distancing. Let’s do this! And get it over with. I want antibodies NOW!