Researchers at the Department of Energy’s Oak Ridge National Laboratory have used Summit, the world’s most powerful and smartest supercomputer, to identify 77 small-molecule drug compounds that might warrant further study in the fight against the SARS-CoV-2 coronavirus, which is responsible for the COVID-19 disease outbreak.
The two researchers performed simulations on Summit of more than 8,000 compounds to screen for those that are most likely to bind to the main “spike” protein of the coronavirus, rendering it unable to infect host cells. They ranked compounds of interest that could have value in experimental studies of the virus. They published their results on ChemRxiv.
The idea was born out of an interest in the coronavirus’ entry point into a host cell. When Chinese researchers sequenced the virus, they discovered that it infects the body by one of the same mechanisms as the Severe Acute Respiratory Syndrome, or SARS, virus that spread to 26 countries during the SARS epidemic in 2003. The similarity between the two virus structures facilitated the study of the new virus.
Jeremy C. Smith, Governor’s Chair at the University of Tennessee and director of the UT/ORNL Center for Molecular Biophysics, worked from the assumption that the two viruses may even “dock” to the cell in the same way.
Team member and UT/ORNL CMB postdoctoral researcher Micholas Smith built a model of the coronavirus’ spike protein, also called the S-protein, based on early studies of the structure.
The compound, shown in gray, was calculated to bind to the SARS-CoV-2 spike protein, shown in cyan, to prevent it from docking to the Human Angiotensin-Converting Enzyme 2, or ACE2, receptor, shown in purple. Credit: Micholas Smith/Oak Ridge National Laboratory, U.S. Dept. of Energy
“We were able to design a thorough computational model based on information that has only recently been published in the literature on this virus,” Smith said, referring to a study published in Science China Life Sciences.
After being granted computational time on Summit through a Director’s Discretionary allocation, Smith used a chemical simulations code to perform molecular dynamics simulations, which analyze the movements of atoms and particles in the protein. He simulated different compounds docking to the S-protein spike of the coronavirus to determine if any of them might prevent the spike from sticking to human cells.
“Using Summit, we ranked these compounds based on a set of criteria related to how likely they were to bind to the S-protein spike,” Smith said.
The team found 77 small-molecule compounds, such as medications and natural compounds, that they suspect may be of value for experimental testing. In the simulations, the compounds bind to regions of the spike that are important for entry into the human cell, and therefore might interfere with the infection process.
After a highly accurate S-protein model was released in Science, the team plans to rapidly run the computational study again with the new version of the S-protein. This may change the ranking of the chemicals likely to be of most use. The researchers emphasized the necessity of testing of the 77 compounds experimentally before any determinations can be made about their usability.
“Summit was needed to rapidly get the simulation results we needed. It took us a day or two whereas it would have taken months on a normal computer,” said Jeremy Smith. “Our results don’t mean that we have found a cure or treatment for the Wuhan coronavirus. We are very hopeful, though, that our computational findings will both inform future studies and provide a framework that experimentalists will use to further investigate these compounds. Only then will we know whether any of them exhibit the characteristics needed to mitigate this virus.”
Computation must be followed by experiment. Computational screening essentially “shines the light” on promising candidates for experimental studies, which are essential for verifying that certain chemicals will combat the virus, according to Jeremy Smith. The use of a supercomputer such as Summit was important to get the results quickly.
This research was funded by the Laboratory Directed Research and Development program and used resources of the OLCF, a DOE Office of Science User Facility located at ORNL.
UT-Battelle manages Oak Ridge National Laboratory for DOE’s Office of Science, the single largest supporter of basic research in the physical sciences in the United States. DOE’s Office of Science is working to address some of the most pressing challenges of our time. For more information, visit energy.gov/science. – Rachel Harken
In the case of a pandemic, I would be looking a non-prescription interaction to stop the virus….or to stop replication.
There are a number of natural antivirals….Oregano. …
Sage. …
Basil. …
Fennel. …
Garlic. …
Lemon balm. …
Peppermint. …
Rosemary….
I’d probably look at fennel since it’s used in Ayruvedic medicine for respiratory problems….but I’m an engineer.
Not a CVS personality…..looking to score the big one off of someone’s epidemic.
Actually one last thing. Serrapeptase was useful to me once with some sort of a weird viral interaction about 6 years ago. The phlegm in my lungs was very sticky…..like it contained protein or some sort of organic-excretion from lung tissue………..and I couldn’t breathe.
I took a couple of capsules and my phlegm returned to normal watery kinda stuff…….the phlegm never had a color from a bacterial infection. Serrapeptase is derived from silk worms. They use it to digest the material of their cocoons when they go through metamorphosis…..people use it for scar tissue removal….strictures around joints from injury….. see also NIH, Japanese research.
Totally true William. I took it for Lyme Disease as well to break up the biofilms. I was searching for ace 2 receptors and ended up here. R&D WORLD. 🙏
I second serrapeptase. I came down with h1n1 and it was the one thing I knew made the biggest difference in ease of symptoms AND recovery time. Also used it to recover from a shingles outbreak in 4 days. Unheard of!!!
Serrapeptase! Used for emphysema, it solves phlegm and inflammation not to mention , from what little info is available online, it degrades biofilm of bacteria and virus, when taken with anitbiotics it has proven to be very very effective, quoting online research here? Side effects very few if any?
I have taken Serrapeptase for 4 years . It has controlled my IPF to the point I no longer need oxygen supplemental support.
Does Serrapeptase make your nose bleed? I only take a once and a while b/c it makes my nose bleed. What about the probiotic VSL #3. I think that helps with fighting the flu.
my husband had a stroke due to blood clot. someone suggested after 7 months of blood thinner to give him serrapeptase. within 3 weeks the cat scan shown the blood clot gone. i told my chiro and she told me i should take it b/c of asthma symptoms. she could not tell me how many a day..the bottle says one , but when my hubs was a time bomb i gave him 2 am and 2 pm it was suggested by a herbalist, i have not found any info on how many i should take….BTW i still have my hubs on 2 am b/c his heart is a bit blocked. no side effects for either of us
I got Covid in June 2020, it’s now October and I’m still fatigued and get winded easy, my pre-existing blood pressure is now hard to control even with Losartan and beta blockers. I am also having chest pain and pressure daily without any exertion. I’ve started taking Serrapeptase 120,000 spu, I take 3 of them at 2am and my 2nd bottle is on it’s way. I’m taking such a large dose as I’m 55 and I’m sure I have arterial plaque and I need to clear it out ASAP, I have no insurance and am scared I am heading for a heart attack or stroke. I’ve been taking the Serrapeptase for about 2 weeks and only thing I’ve noticed is in the #2 department, wow that stuff cleans you out.
I am also going to start taking Garlic and adding food grade Diatomaceous Earth to my protein shakes, I’ve taken this years ago safely and DE is basically microscopic silica (glass) that clears out not only the gut but gets in the blood stream and clears out plaque and clots.
Serrapeptase / Serretia is wonderful. I take it to prevent symptoms of rheumatoid arthritis – plus a proprietary mix of enzymes and anti-inflammatory natural elements such as bromelain – also from Arthur Andrews – Neprinol. I have been taking them for a few years now and luckily caught the disease before it had done any real damage. The capsules take a while to kick in – about three to four months in my case – but they heal rather than suppress symptoms. I added high concentrate rosehip extract into the mix and I’ve very little problem now and rarely any pain or stiffness. I have occasional short but manageable flares – due to stress usually – but only in smaller joints – fingers and feet. I’m very active and have been able to resume all of my exercise activities as normal – swimming, walking and dancing. Because of the way it works, I’ve been wondering if serrapeptase has properties that are protective as far as the coronavirus effects us – looks like that is probable.
I believe the main thing to help beat this infection is for all of us to strengthen our immune system; diet, supplements, exercise, sleep.