Tuesday, March 24, 2020

IBM Supercomputer Summit identified possible drug compounds for COVID19 vaccine

Humanity is going through difficult time. It's important for us to fight COVID19 together. The world is facing an unprecedented challenge with communities and economies everywhere affected by the growing COVID-19 pandemic. The world is coming together to combat the pandemic bringing governments, organizations from across industries and sectors to help respond to this global outbreak. That means unleashing the full capacity of our world-class supercomputers to rapidly advance scientific research for treatments and a vaccine. IBM announced an initiative to increase access to high-performance computing for groups researching and fighting the novel coronavirus, also known as COVID-19. Scientists have enlisted the help of a supercomputer to fight back against the rapid spread of the novel coronavirus. Researchers from the Oak Ridge National Laboratory just published the results of a project in which they tasked the massive IBM supercomputer known as Summit with finding the most effective existing drugs that could combat COVID-19. Summit [described as Formula One of supercomputers], can perform mathematical equations at speeds that “boggle the mind” i.e Capable of performing over 200 quadrillion calculations per second . That’s not a typo :)- .  This computation speed  accelerates the process of discovery. More details on system specifications available at link

Vaccine and Drug development is the process of bringing a new infectious disease vaccine or therapeutic drug to the market once a lead compound has been identified through the process of drug discovery, typically requiring more than five years to assure safety and efficacy of the new compound. Supercomputers can solve calculations and run experiments that, if done on traditional computing systems or by hand, would take months or years. In traditional computing systems and data centers, each computer functions and does calculations independently. By contrast, high-performance computers can work together and pass calculations between one another to process information more quickly. Such computers are also especially good for conducting research in areas like epidemiology and molecular modeling because the systems mirror the interconnectivity that exists in nature.

IBM partnered with the White House Office of Science and Technology Policy and the Department of Energy to create the COVID-19 High Performance Computing Consortium. The effort, which IBM started just last week, is expected to harness powerful high-performance computing, or “supercomputing,” resources that will massively increase the speed and capacity of coronavirus-related research. The COVID-19 High-Performance Computing Consortium includes the Seattle area’s powerhouses of cloud computing, Amazon Web Services and Microsoft, as well as IBM and Google Cloud. There are also academic partners (MIT and Rensselaer Polytechnic Institute), federal agency partners (NASA and the National Science Foundation) and five Department of Energy labs (Argonne, Lawrence Livermore, Los Alamos, Oak Ridge and Sandia). Among the resources being brought to bear is the world’s most powerful supercomputer, the Oak Ridge Summit, which packs a 200-petaflop punch. The system will harness 16 supercomputing systems from IBM, national laboratories, several universities, Amazon, Google, Microsoft and others. Computing power will be provided via remote access to researchers whose projects are approved by the consortium’s leadership board, which will be comprised of tech industry leaders and White House and Energy Department officials. The group plans to begin accepting research proposals through an online portal.



US Department of Energy’s Oak Ridge National Laboratory(ORNL)  has deployed the world’s most powerful and smartest supercomputer, the IBM built Summit, in the fight against COVID-19. Researchers from ORNLwere granted emergency computation time on Summit, using it to perform simulations with unprecedented speed. In just 2 days Summit identified and studied 77 small-molecule drug potential compounds to fight against the COVID-19 (new Coronavirus). A task that – using a traditional wet-lab approach – would have taken years. The researchers at Oak Ridge National Laboratory used Summit to perform simulations of more than 8,000 possible compounds to screen for those that have the most opportunity to have an impact on the disease, by binding to the main “spike” protein of the coronavirus, rendering it unable to infect host cells. Starting with over 8,000 compounds, Summit’s incredible power shortened the time of the experiment dramatically, ruling out the vast majority of possible medications before settling on 77 drugs which it ranked based on how effective they would likely be at halting the virus in the human body.

The paper, which was published in the journal ChemRxiv, focuses on the method the virus uses to bind to cells. Like other viruses, the novel coronavirus uses a spike protein to inject cells. Using Summit with an algorithm to investigate which drugs could bind to the protein and prevent the virus from doing its duty, the researchers now have a list of 77 drugs that show promise. They ranked the compounds of interest that could have value in experimental studies of the virus[source]


Whats  mutation and  Features, Evaluation with respect to  COVID19 ?


Structure of the Coronavirus Virion
Mutation is a mundane aspect of existence for many viruses, and the novel coronavirus is no exception. This new virus COVID19 which is the acronym of "coronavirus disease 2019" seems to be very contagious and has quickly spread globally.The CoVs have become the major pathogens of emerging respiratory disease outbreaks. They are a large family of single-stranded RNA viruses (+ssRNA) that can be isolated in different animal species. For reasons yet to be explained, these viruses can cross species barriers and can cause, in humans, illness ranging from the common cold to more severe diseases such as MERS and SARS. The potential for these viruses to grow to become a pandemic worldwide seems to be a serious public health risk.

A mutation is an alteration in the nucleotide sequence of the genome of an organism, virus, or extrachromosomal DNA. Mutations result from errors during DNA replication, mitosis, and meiosis or other types of damage to DNA. The RNA viral genome can be double-stranded (as in DNA) or single-stranded.  In some of these viruses, replication occurs quickly, and there are no mechanisms to check the genome for accuracy.  This error-prone process often results in mutations.  You can think of COVID19 and probably next mutated version COVID20  :) . A gene mutation is a permanent alteration in the DNA sequence that makes up a gene, such that the sequence differs from what is found in most people. Replication errors and DNA damage are actually happening in the cells of our bodies all the time.In most cases, however, they don't cause cancer, or even mutations. That's because they are usually detected and fixed by DNA proofreading and repair mechanisms. 

CoVs are positive-stranded RNA viruses with a crown-like appearance under an electron microscope (coronam is the Latin term for crown) due to the presence of spike glycoproteins on the envelope. The subfamily Orthocoronavirinae of the Coronaviridae family (order Nidovirales) classifies into four genera of CoVs: Alphacoronavirus (alphaCoV), Betacoronavirus (betaCoV), Deltacoronavirus (deltaCoV), and Gammacoronavirus (gammaCoV). Furthermore, the betaCoV genus divides into five sub-genera or lineages.[2] Genomic characterization has shown that probably bats and rodents are the gene sources of alphaCoVs and betaCoVs. On the contrary, avian species seem to represent the gene sources of deltaCoVs and gammaCoVs.  Members of this large family of viruses can cause respiratory, enteric, hepatic, and neurological diseases in different animal species, including camels, cattle, cats, and bats. To date, seven human CoVs (HCoVs) — capable of infecting humans — have been identified.  

SARS-CoV-2 belongs to the betaCoVs category. It has round or elliptic and often pleomorphic form, and a diameter of approximately 60–140 nm. Like other CoVs, it is sensitive to ultraviolet rays and heat. Furthermore, these viruses can be effectively inactivated by lipid solvents. Its single-stranded RNA genome contains 29891 nucleotides, encoding for 9860 amino acids. Although its origins are not entirely understood, these genomic analyses suggest that SARS-CoV-2 probably evolved from a strain found in bats. The potential amplifying mammalian host, intermediate between bats and humans, is, however, not known. Since the mutation in the original strain could have directly triggered virulence towards humans, it is not certain that this intermediary exists. Because the first cases of the CoVID-19 disease were linked to direct exposure to the Huanan Seafood Wholesale Market of Wuhan, the animal-to-human transmission was presumed as the main mechanism. Nevertheless, subsequent cases were not associated with this exposure mechanism. Therefore, it was concluded that the virus could also be transmitted from human-to-human, and symptomatic people are the most frequent source of COVID-19 spread. The possibility of transmission before symptoms develop seems to be infrequent, although it cannot be excluded. Moreover, there are suggestions that individuals who remain asymptomatic could transmit the virus. This data suggests that the use of isolation is the best way to contain this epidemic. As with other respiratory pathogens, including flu and rhinovirus, the transmission is believed to occur through respiratory droplets from coughing and sneezing.
source

The novel SARS-CoV-2 coronavirus [COVID19] that emerged in the city of Wuhan, China, last year and has since caused a large scale COVID-19 epidemic and spread all over the world is the product of natural evolution. The scientists analyzed the genetic template for spike proteins, armatures on the outside of the virus that it uses to grab and penetrate the outer walls of human and animal cells. More specifically, they focused on two important features of the spike protein: the receptor-binding domain (RBD), a kind of grappling hook that grips onto host cells, and the cleavage site, a molecular can opener that allows the virus to crack open and enter host cells. A recent scientific article suggested that the novel coronavirus responsible for the Covid-19 epidemic has mutated into a more "aggressive" form. The genetic material of the virus is RNA. Unlike with human DNA, when viruses copy their genetic material, it does not proofread its work. Because RNA viruses essentially operate without a spell-check, they often make mistakes. These "mistakes" are mutations, and viruses mutate rapidly compared to other organisms. Mutations that are harmful to the viruses are less likely to survive and are eliminated through natural selection. Sadly, this new virus doesn’t have that deletion. When mutations occur that help a virus spread or survive better, they are unlikely to make a big difference in the course of an outbreak. Still, a common perception is that the continuous acquisition of mutations will cause our future coronavirus vaccines to be ineffective. While virus evolution may confer vaccine resistance, this process often takes many years for the right mutations to accumulate. A virologist at the Charité University had sequenced the virus from a German patient infected with COVID-19 in Italy. The genome looked similar to that of a virus found in a patient in Munich; both shared three mutations not seen in early sequences from China But he thought it was just as likely that a Chinese variant carrying the three mutations had taken independent routes to both countries.  Like all viruses, SARS-CoV-2 evolves over time through random mutations, only some of which are caught and corrected by the virus’s error correction machinery. Scientists will also be scouring the genomic diversity for mutations that might change how dangerous the pathogen is or how fast it spreads. There, too, caution is warranted.
 


 Why a supercomputer is needed to fight the coronavirus  [COVID19]:
 
Viruses infect cells by binding to them and using a ‘spike’ to inject their genetic material into the host cell. To understand new biological compounds, like viruses, researchers in wet labs grow the micro-organism and see how it reacts in real-life to the introduction of new compounds. This is a slow process without powerful computers that can perform digital simulations to narrow down the range of potential variables. Computer simulations can examine how different variables react with different viruses. Each of these individual variables can comprise billions of unique data points. When these data points are compounded with multiple simulations, this can become a very time-intensive process if a conventional computing system is used.


These promising compounds could now play a role in developing new treatments or even a highly-effective vaccine that would keep the virus from taking root inside a person’s body. Right now, our best defense against the virus is social distancing, but a vaccine or treatment to ease symptoms and shorten recovery time would go a long way toward getting us on track for a return to normalcy. Researchers used the supercomputer to screen 8,000 compounds to identify the 77 most likely to bind to the main “spike” protein in the coronavirus and render it incapable of attaching to host cells in the human body. Those 77 compounds can now be experimented on with the aim of developing a coronavirus treatment. The supercomputer made it possible to avoid the lengthy process of experimenting on all 8,000 of those compounds


The results from Summit don’t mean that a cure or treatment for the new coronavirus has been found. But scientists hope that the computational findings will inform future studies and provide a focused framework for wet-labs to further investigate the compounds. Only then will we know if any of them have the needed characteristics to attack and kill the virus. Going forward, the researchers plan to run the experiment again with a new, more accurate model of the protein spike that the virus uses. It’s possible that the new model will change which drugs are most effective against the virus and hopefully shorten the road to a treatment option. It will still be many months before we have a vaccine available, but scientists are hard at work on those solutions. IBM said Summit would continue to be used for "providing ground-breaking technology for the betterment of humankind".
Reference:
https://www.ibm.com/blogs/nordic-msp/ibm-supercomputer-summit-attacks-coronavirus
https://nypost.com/2020/03/23/supercomputer-finds-77-drugs-that-could-halt-coronavirus-spread
https://www.mercurynews.com/2020/03/22/ibm-partners-with-white-house-to-direct-supercomputing-power-for-coronavirus-research

https://www.ncbi.nlm.nih.gov/books/NBK554776
https://www.youtube.com/watch?v=NJLXdsO1GBI
https://www.youtube.com/watch?v=PWzbArPgo-o

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