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Structural Biology

Structure of novel coronavirus spike protein solved in just weeks

Cryo-EM structure of key coronavirus protein could help develop vaccines against the virus

by Laura Howes
February 19, 2020 | APPEARED IN VOLUME 98, ISSUE 8

 

09808-scicon3-spike.jpg
Credit: Jason McLellan/University of Texas at Austin
Side view of the SARS-CoV-2 spike protein with one receptor binding domain shown in colored ribbons.

In an incredibly fast piece of research, scientists from the University of Texas at Austin and the National Institutes of Health have released a cryo-electron microscopy (cryoEM) structure of part of SARS-CoV-2, the novel coronavirus that has infected tens of thousands of people and killed more than 2,000 since the end of December (Science 2020 DOI: 10.1126/science.abb2507).

The part of the virus imaged, called the spike protein, helps the virus attach to and infect human cells, and its structure comes just weeks after the virus’s genome sequence was published. The breakthrough is a huge step toward developing a vaccine against the virus as well as treatments for COVID-19, the disease that it causes, the researchers say.

UT Austin’s Jason McLellan and his colleagues have spent many years studying other coronaviruses and had already figured out how to use select mutations to lock coronavirus spike proteins into a shape that is conducive for structural studies. After they got the genome sequence of the virus, it took the team just two weeks to design and produce samples of the stabilized spike protein. After collecting data on their stabilized spike protein samples using a cryo-electron microscope, the researchers spent 12 days reconstructing the 3-D structure. They published the results on bioRXiv on Feb. 15, and the paper was rushed through peer review before being published by Science on Feb. 19 (DOI: 10.1126/science.abb2507).

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“This is stunning work, illustrating the power of molecular biology in combination with cryoEM,” says Alice Clark, a structural biologist at the University of Wolverhampton. “How quickly this work was possible is a credit to both the scientists involved in this structure, and the recent advances in cryoEM as a technique.”

Coronaviruses are RNA viruses that typically enter human cells when their glycoproteins bind proteins on the cell surface. SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) on human cells with higher affinity than does the virus that caused severe acute respiratory syndrome (SARS) in 2003. This difference in affinity possibly explains why the novel coronavirus is more contagious than that other virus. The team is already testing the stabilized spike as a vaccine, and hope the structure will help in the development of antivirals. Similar studies on spike proteins from SARS and Middle East respiratory syndrome (MERS) viruses were used to develop experimental vaccines, but the vaccines never made it to market.

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Comments
Chika (February 27, 2020 8:38 AM)
This is a welcome development in the face of the fears and concerns generated about the deadly virus. Thank God for the advances in cryoEM and molecular biology. The fact that the virus is an RNA virus makes its impact on cell invasion more devastating. Congratulations to the scientists responsible for the development of the molecular structure if the virus. Well done.
Darlene Ashleah Gedge (March 2, 2020 2:17 AM)
Informative
Justin (March 4, 2020 11:58 PM)
As a citizen of United States, I am concerned about the virus spreading to more and more people. I have warned my family and will keep note of all that is going on!
greg (May 12, 2020 11:32 AM)
It's not a matter of "if" but "when" we will get it. A majority of us have had it, currently have it or just waiting to have it. With human interaction it is just a matter of time. some of us are already immune to it.
Tofazzal Hossain (March 10, 2020 4:31 AM)
drthossain65@gmail.com
I am from Bangladesh. I am also concerned this virus.Sometimes spread this virus but we prevent it by health education and keep cleanliness our environment.
R.K.Singh (March 13, 2020 6:32 AM)
I must congratulate the scientists for their prompt action and initiative on deadly CORONA Virus. I hope Scientists will find out effective control measures very shortly.
Bosun Banjoko (March 14, 2020 9:10 AM)
The progress made so far is outstanding, The next stage is clinical trials of ACE inhibitors in infected persons and the development of vaccines directed against the spike protein used for attachment to the host cells by the virus.
Geeta bhati (March 15, 2020 1:06 AM)
Drinking a teaspoon of Buffalo's ghee at early morning i.e at empty stomach may help to reduce the effect of Corona virus. I kindly request you to try this on some patients effected by Corona virus.
gurupada chakravorty (May 1, 2020 9:55 AM)
I was viewing some news on wuhan which were telecasted on opening the normal life there after Covid errupted . I saw a group of monkeys were on the heap of Papaya pieces cuts into two with all seeds removed.I had a string believe that papaya seeds chewing could play effective role in fighting against Corona
mark a coffey (March 21, 2020 6:53 AM)
Using the technology left to us at the Wardenclyffe Tower....why not use that technology to create a horn antenna to use with existing power lines, to resonate a frequency on a nation wide scale that is set at the same quantum vibration that holds it glycoproteins together. If the virus glycoproteins are disabled, then it can not attach itself to a cell.

Once the frequency is resonating through the power lines, you can then easily install a horn antenna to the transformer to resonate the frequency in the open. The same type device can be created for wall outlets to resonate in people's homes. This will effect any of the virus that is contaminating surfaces. Combine that with social distancing, and we could greatly reduced the spread while the vaccine to kill it is being created.
Ayush (March 21, 2020 2:23 PM)
Stablizing the composition of spike cell is great. But, what we need to ensure that stabilizing spike protein of a cell is effective for everyone and for every organ. Although all human cells fundamentally develop from the same place. But, the composition of each human cell is different for every organ. The cell composition also varies in levels of structures. Also, we have to keep in mind about the pathogens which builds our immune system stronger over the generations and time. If a virus enters your body or your cells start deforming due to increased levels of the comprising stuctures, it will cause dysfunction in your body and your pathogens will not be able detect the virus to fight back.
We need to make sure that our body parasites are able to stop the dysfunctional spiked protein cell from spreading. I think you should try to find test the cells of mild Corona virus patients and do blood test to ensure how the pathogens react to it. If you can find even one individual who recovered from coronavirus, then you can test how this virus reacted in their body and make changes accordingly to what you develop.
Rajiv Kumar (March 21, 2020 11:28 PM)
What is the chemical formula of the novel corona. It can be end by making it's apposite chemical ponding
Faik A K Nasser (March 24, 2020 12:03 PM)
While we must find vaccine to boost immune
system based on the structure of Coronavirus spike
Protein we must promote the value of antioxidants in ascorbic acid coupled with glutathione and Glutothion reductase through increasing the availability of GSH in high concentration against GSSG by Maintaining homeostasis GSH/GSSG. can be achieved by eating vitamin rich fruits & vegetables and plenty of sulfur rich food.
JOYDEV PANDEY (March 22, 2020 10:43 AM)
THE DESCRIPTIONS ILLUSTRATED ABOVE WILL HELP ANY BIOLOGIST TO KNEW DETAILS ABOUT CORONAVIRUS . I WANT TO KNOW ONE THING WHICH IS IN MY MIND THAT IF WE IN GENERAL GOES FOR TEST AND TAKE THE PRECAUTION TO OUR RESPIRATORY TRACT BY GENTAMYCIN OR TOBRAMYCIN , THEN IT WILL BE BENEFICIAL FROM CORONA INFECTION...PLEASE HELP ME BY GIVING ANSWER.ANOTHER THING IS ALSO ABOUT 'DIPALNITOPHOSPHATIDYLCHOLINE'- AN ESSENTIAL PROTEIN COAT OF ALVEOLI OR RESPIRATORY TRACT -ANY HOW IF IT CAN BE ENRICHED. PLEASE GIVE ME IDEAS ABOUT THESE
Bijoy Das (May 21, 2020 12:52 PM)
The drugs you have mentioned are antibiotics which are effective only against Upper Respiratory tract infections. A retrovirus like SARS type 2 corona virus requires anti retroviral therapeutic drugs akin to the treatment of AIDS. Either the bilipid cell wall has to be ruptured or the spikes changed to such a shape tht they cannot attach to the Angiotensin converting hormone which has receptors for the viral proteins. The cell wall rupture occurs with the oral administration of hydroxyquinol. Symptomatic treatment may be given concomitantly.
dhanush (March 22, 2020 12:50 PM)
please save this world by inventing antidot for it as early as possible.you(scientists) are the real gods
RIYA Gupta (March 23, 2020 2:42 PM)
I dont have any knowledge about this viruses but as a common human as we know washing our hands with soap n water for 20 seconds or with alcohol based sanitizer we can kill it from our hands .so is it possible that using chemical formula of these two or any one of it one can find its antidote. As i heard that soap breaks fats n proteins found in dust n virus n this virus is also made up of proteins .
Priyanka Kharbas (March 24, 2020 7:59 AM)
1.When the virus come for binding ... the receptors on our body plays an important role ... if we could change the receptor mechanism... which is difficult bt not impossible than even if virus comes on our body cannot bind us.
2. Its spike has protein ... protein when coagulated is virus will be killed
Duro Koruga (March 24, 2020 10:13 PM)
What is coronavirus the number of spikes?
What is symmetry of coronavirus?
Somnath Paul (March 25, 2020 12:03 AM)
I'm from India. Can you please send me the chemical structures of COVID-19 in details please.
Chandan kumAr (April 7, 2020 5:44 AM)
Hi plzzz send me also structure formula of corona virus
Ok
Keep it up
dale r hunt (April 2, 2020 10:12 PM)
can this virus live in a 20 in vacuum ? if can not could ppe be sanitized this way
Emily h (April 6, 2020 8:29 PM)
This is very good for my 8th grade students!!!♡♡♡♡♡♡♡♡♡♡♡♡♡♡♡♡♡♡♡♡♡♡♡♡
DR NIHAL DESILVA (April 16, 2020 2:24 PM)
THERE IS NO STRUCTURAL FORMULA FOR THE VIRUS!!?? THERE ARE MOLECULAR STRUCTURES OF THE SPIKE PROTEIN & OTHER PROTEINS!! THESE ARE HUGE & MANY KDALTONS!! WHY U NEED THIS??
John Hache (April 24, 2020 1:39 AM)
Now that we know that the spike protein is the major element required to enter the cell, in quantum physics we understand that this protein also has its own signature or resonance frequency. Once the frequency identified we should be able to disarm it using its opposing destructive frequency. Please advise if this is possible. In Israel they are already using ultraviolet light with huge success. Of course ultraviolet light is also a frequency. The proper form of this light will circumvent ozone production. Ozone production is one reason why it has been overlooked. This would be faster and more effective than any vaccine.
Allotey Abdul Latif (May 17, 2020 6:18 AM)
What are some four major proteins or enzymes in the SARS COV2
Also, some drugs which have been used to treat coronavirus
MBADEKA (June 23, 2020 12:28 AM)
I think binding of covid 19 molecule with other molecule in the body and creating infection in the lungs can be stopped by reacting these molecules with some organic acids such as citric acid. Drinking hot lemon water may help.
We must think how chemical reaction of covid 19 molecule can be stopped with our body's cells by getting reacted covid 19 with external chemical.
Some research is required on this chemical phenomena.
Regards
MBADEKA
Dany (July 4, 2020 11:46 AM)
If you get it through mouth than acid can work. However, in case you get it by nose or eyes, in that case citric acid won't work. In that case we need some inhaling spray to kill it.
Allen (July 1, 2020 1:10 AM)
Is there only one type of protein spike on the surface of the SARS COV2 virus?
If not, how many are there actually?
I imagine there are many more, which allows it to infect multiple species of animals.
I imagine some of these are identical to those on other coronavirus surfaces, making it difficult for an antibody test to distinguish a SARS COV2 antigen from our immune antigens for other coronaviruses.
Could this explain why antibody tests are not nearly as accurate as hoped?

Is there only one type of protein that will bind to the ACE2 portal into the human respiratory cell?
Is there only one type of antibody protein that will bind to the SARS COV2 virus spike which matches ACE2?
If so, do the antibody tests look for all of them?
Dan (July 20, 2020 11:57 AM)
Is it possible for foods such as walnuts ( they contain a peptide with ACE 2) to prime the body almost like an anti-vaccine? So your T cells would not recognise coronavirus at least not the t2 allergen response ...? I find it curious that the top walnut consuming countries were first to be infected also just after the holidays when walnut consumption was highest. Given walnuts contain this peptide, my gut feel is this "priming " is possible but I am not really sure?

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