Computational modeling yields a protein fragment that could bind to coronavirus spike proteins and destroy them.
The research described in this article has been published on a preprint server but has not yet been peer-reviewed by scientific or medical experts.
Using computational models of protein interactions, researchers at the MIT Media Lab and Center for Bits and Atoms have designed a peptide that can bind to coronavirus proteins and shuttle them into a cellular pathway that breaks them down.
This type of peptide could hold potential as a treatment that would prevent the SARS-CoV-2 virus from reproducing itself within infected cells, the researchers say.
“Our idea was to use computational techniques to engineer a peptide that could be a therapeutic for COVID-19. Once the peptide gets in the cell, it can simply tag and degrade the virus,” says Pranam Chatterjee, a recent MIT PhD recipient and the lead author of the study.
The researchers have tested the peptide in human cells, and they are now planning additional cell and animal studies to further evaluate its efficacy. They reported their initial findings in a preprint posted on bioRxiv, an online preprint server, on June 1, and have also submitted it to a peer-reviewed journal. Graduate student Manvitha Ponnapati and Joseph Jacobson, an associate professor in the MIT Media Lab, co-authored the study.
Scientists are pursuing many different strategies to develop new therapeutics against SARS-CoV-2. One area of interest is developing antibodies that bind to and inactivate viral proteins such as the spike protein, which coronaviruses use to enter human cells. A related approach uses small protein fragments called peptides instead of antibodies.
The MIT team set out to engineer peptides that could strongly bind to the spike protein inside cells, and to use these peptides to trigger the cells to break down the viral proteins. Their idea was to have their peptides recruit naturally occurring proteins called E3 ubiquitin ligases, which can mark proteins for destruction when cells no longer need them.
To generate their spike-protein-binding peptides, the researchers used a computational model of protein interactions that they had previously trained to optimize binding strength between two proteins. Chatterjee and others recently used similar computational methods to design improved versions of enzymes used for the genome-editing technique known as CRISPR. Their new CRISPR-Cas9 enzymes, together, can target more than 70 percent of DNA sequences, while the most commonly used form of CRISPR-Cas9 reaches only about 10 percent.
In this case, the researchers used as their starting point the human ACE2 protein, which is found on the surface of certain types of human cells and binds to the coronavirus spike protein.
They used their model to break ACE2 into many small fragments and then computationally predict how the fragments would interact with the spike protein. They instructed the model to optimize three features: First, they engineered peptides to have strong binding affinity to the spike protein. Second, they established that the peptides could bind well to other coronavirus spike proteins, in hopes that it could work against past and future strains of coronaviruses. Third, they ensured that the peptides would not bind strongly to human proteins called integrins, which are the proteins that normally bind to the ACE2 receptor in the body.
This process generated about 25 candidate peptides, which the researchers fused to an E3 ubiquitin ligase and tested in human cells that expressed a fragment of the spike protein known as the receptor-binding domain (RBD).
The best of these candidates, a 23-amino-acid peptide, broke down about 20 percent of the RBD proteins in the cells. However, this peptide did not work as well as the original ACE2 protein, which broke down about 30 percent of the RBD proteins. To improve the peptide’s performance, the researchers used their model to simulate how its RBD-binding would be affected if they substituted different amino acids at each of its 23 positions. That optimization process yielded a mutant peptide that improved the degradation rate to over 50 percent.
Tagged for destruction
One key advantage of this peptide is its small size — even when fused to the E3 ubiquitin ligase, the entire chain is only around 200 amino acids in length. The researchers envision that RNA or DNA encoding the peptides could be delivered by harmless viruses called adeno-associated viruses.
Another possibility would be to deliver the peptide on its own, allowing it to bind to the coronavirus spike protein outside of cells and be carried into cells with the virus. In that case, the virus would then be tagged for destruction as soon as it enters the cell, Chatterjee says.
The researchers are now planning to test the peptide in human cells infected with the SARS-CoV-2 virus, which will occur at specialized biosafety labs outside MIT. If those tests are successful, the researchers hope to test the peptide in animal models. They are also working on further improving the peptide so that it can bind the spike protein more strongly.
This work was supported by the consortium of sponsors of the MIT Media Lab, the MIT Center for Bits and Atoms, and Jeremy and Joyce Wertheimer.
The brain is a biological computer that can manufacture all of us and every living thing on Earth. Each species has a unique brain that takes the food the we give ourselves and makes us whatever we may be biologically programed to be. If the human body needs 9 different amino acids to create all the different kinds of cells that the body needs to make us then why not give the body the 9 different amino acids in every day meals to ourselves and see what happens because then that biological computer in our minds can then maybe have the cure for fighting the coronavirus and all it needed was the combination of all those 9 amino acids in our food daily to make the cells to overtake the damage that the coronavirus can cause. There is a recipe for a food dish called Adelynn’s Miracle Beans recipe that has all the 9 different amino acids as well as many other nutrients the body needs. Perhaps if we were to give those that are sick from coronavirus 2 servings of this Adelynn’s Miracle Beans recipe daily 5-6 hours apart and also give 2 Centrum equivalent vitamins with a bean meal 5-6 hours apart. This will give one’s body all the proteins, vitamins and minerals that a human body needs to create any kind of blood cell. Maybe the human body will figure out a way to kill the coronavirus as well as other flues and colds if we give it the ingredients for it to do so! Someone try it. It beats dying or suffering from the illness. I know that taking 2 Centrum equivalent in one day with a meal 5 hours apart does help one get rid of the flu and colds because I have been doing it for 25 years and it always help me stop getting sicker every time I felt like I was getting the flu. So maybe eating Adelynn’s Miracle Beans and taking the vitamins will help make people with the coronavirus get better.
More thoughts about the coronavirus situation. Being that certain filters can catch the coronavirus in the air and stop it from spreading around I would assume that these filters are at this day and age currently installed in all nursing homes and hospitals. However being that the coronavirus is rapidly spreading in hospitals and nursing homes it is obvious we have to up our game when we use filters that can stop the coronavirus as well as other viruses and germs. We now have the need and desire to design ways to use filters and ultra violet light and laser treated copper and any other stuff to stop the coronavirus from being in the indoor air at everywhere we are be it home, work, school, store, office, hospital, nursing home, sporting events and everywhere else we live or work in. To stop the spreading of the coronavirus by air must be a major goal of ours. If we can stop the spread of coronavirus by air then we will have to only stop the coronavirus by touch which is a lot easier task than doing things to stop the air transmission of the coronavirus as well as other germs and viruses. To stop the coronavirus by touch can be done by cleaning and handwashing and using new practices that insures that you wipe your hands every time you touch something. Oh, and most important, DON”T touch your mouth or nose! Think of this coronavirus thing as a cross contamination game. A person gets the coronavirus. That person can spread it around through the air and whatever droplets of body fluids that person leaves around which then is touched by someone else who then transfer that coronavirus molecule into their body by way of mouth, nose, and maybe eyes too. So this is the world we live in and we have to figure out better ways to live in it! We have to put air ventilators everywhere that can stop the coronavirus. We have to do this immediately in hospitals, nursing homes, schools, elevators, stairways, lobbys, businesses and public buildings. These new air ventilators would be numerous in larger settings such as gyms and smaller in places like elevators. There would be different room size systems. It seems that we will have to design new equipment to do all of what I have suggested over my many postings because I’m sure that already we use coronavirus fighting filters in all public ventilation systems. So I believe we now have to make gadgets that can hang about 2 feet over our heads in areas of the rooms that we congregate in inside buildings. These gadgets would suck the air in a intake part of th gadget, run that air through a filter and other things installed in that gadget that will stop the coronavirus. Then the air will exit the gadget with the air free from the coronavirus as well as other germs and viruses. Doing this will insure that the coronavirus and other viruses and germs won’t be spreading around so much which means a lot less people will be getting sick or dying from the coronavirus as well as the flu and colds. Doing this will save lives and misery and money for us all! So let’s get the job started and put on our thinking caps as we figure out ways to get this coronavirus out of our air and off of anything else it may be on! Once we do this people will feel more comfortable going out in public. The businesses that do this first will see will see increased customers quicker as well as healthier workers and patients. Doing this may be the ONLY way we are ever going to get rid of this coronavirus. It will surely cut down on the rate of infection! We can’t rely on a vaccine to save us from this coronavirus as well as other germs and viruses. We can’t rely on the vaccine makers to have to yearly design vaccines to save us from illnesses. For many those vaccines don’t work well enough to prevent illness and death. So it’s time we start using mechanical means to kill the coronavirus as well as other germs and viruses! The sooner we do it the better off we all are!
A few more thoughts about the Coronavirus. We are at a time when we have to have different plans set up about about how to do things that will help you to not catch the Coronavirus. In different parts of the country, counties, cities and neighborhoods we have to now do many things that will insure that we don’t come in contact with the Coronavirus in the many places it can be, be it in the air or on things. Crowded cities like New York have a lot more chances of someone catching the Coronavirus because they are forced to have to live in an environment that requires them to constantly come in contact with people who may have the virus and or touched the surfaces of things that has Coronaviruses droplets on it from the sneezing, coughs, spitting,runny nose droplets put there by hands, nose and mouth of those with the virus. These Coronavirus droplets can live on surfaces for many hours so nobody knows what surfaces are virus free or not. So America, it is time we step up and protect ourselves and do it in a way that will shut down the growth of this virus in the population. Unless we start protecting ourselves better New York and other crowded places are going to have a very hard time eliminating this virus because many of the people who live there reside in buildings that require one to use an elevator or enclosed stairway to get to one’s residence. Elevators are probably one of the places where it is easiest to get Coronavirus because one sick person with Coronavirus that is sneezing or coughing on a long elevator ride can maybe get other people sick on that elevator if they don’t have protection from the coronavirus. So everyone who rides an elevator or walks up enclosed staircases or goes out on errands or to work should be wearing a face mask of some kind or use a paper towel to cover their nose and mouth when they are within 12 feet of people. Also if you are not wearing glasses or have eye contacts on then you should wear those glasses they sell in stores to protect eyes that are clear. Doing these things will ensure that your eyes, nose and mouth is protected from the travelling Coronavirus that was released from someone’s mouth or nose with the virus when they sneezed, cough or touch something. Protect yourselves or you may die or get very sick! In this virus attack era we live in we have to have protection on our breeding aparatis, our mouths and our nose every time we leave our residence to go anywhere. However there is one more thing we must do to protect ourselves. There is another way to contact the Coronavirus and that is TOUCH! You can touch a surface that has the residue of the Coronavirus on it and then transfer that virus to your mouth, nose or face area after which you then transfer the virus into the inside of your body when you then lick your lips or touch in or near your nose’s nostrils where it is then inhaled into your body. That is why it is important to wear disposable gloves when you go out. If you can’t get or afford disposable gloves then use paper towels or toilet paper or any piece of paper to use to touch/turn door knobs, elevator buttons, staircase railings, shopping carts, doors or anything else that someone has also touched. Think of this Coronavirus as a abuch of diarrhea shit that is flying out of Coronavirus stricken people’s mouth that is landing on those around them and the surfaces around them. You wouldn’t want to get any of that shit in your body or touch any of that shit so do the same with the Coronavirus! One more thing, one way to get our economy open again and more people to work is to initiate new ways to go shopping. Stores have to remember that they are themselves are causing their stores to be locked down or causing patrons to be fearful of shopping there because of the closeness that happens when people go into a store to shop. We have to design a better way to shop that doesn’t require us to go into the store to get what we want. We need to initiate curb side shopping! We need to make it so that someone can pull up to a store and a clerk comes out and ask what you want or we can have menus displayed or printed by the business that shows their items for sale. We can then have the store clerk take the order, fill it out and then deliver the items to the parked customer who is parked a space that has distanced between parked cars. The customer can either pay outside the store or drive/ walk up to the front of the store where a device they use in many gas stations that lets the people pay through a glass shield and a metal box slides back and forth between the enclosed store where people pay and pick up their payed for merchandise. We have to come up with new ways to shop that doesn’t require us to mingle together in stores! More later
Another thought about this Coronavirus situation. Hopefully someone is looking into what I have to say but if you, especially you in the medical field, ever look into the possibility that this Coronavirus as well as maybe other unwanted things may be spreading more easily and faster because it has a way of spreading easily by attaching itself onto the mustaches and beards of men. Think about it, this virus can survive for a long time on many different objects and surfaces so why can’t it attach itself to someone’s hairy mustache or beard that it lands on as it was spit or sneezed out of someone’s nose or mouth through a cough or sneeze. Or if someone with a beard or mustache happens to touch a doorknob or any other thing that someone with the virus has left moisture from a cough, sneeze or any moisture or saliva from their body and then that bearded person was to touch their beard or mustache which would transfer the virus on the bearded person’s body which could possibly be licked into the body of the bearded person as that person lick their lips and some hairs around their mouth, which may have the virus lingering there unnoticed just waiting for the next place life will take it as it explores our world!
Welcome to 2020!
PLEASE STOP TESTING ON ANIMALS!!!