Supercomputer Research Leads to Human Trial of Potential COVID-19 Therapeutic Raloxifene

By Oliver Peckham

October 29, 2020

Six months of patient trials with the ostensible COVID-19 therapeutic remdesivir have cast serious doubt on its ability to even reduce the severity of COVID-19, let alone reliably reduce patient mortality. This has left medical professionals once again without a proven COVID-19 therapeutic as the pandemic shows signs of reaching unprecedented spikes in Europe and North America. As the world confronts the possibility of a dark winter, a supercomputer-powered pharmaceutical research coalition based in Italy is producing a glimmer of light: a repurposed drug called raloxifene, identified by supercomputing research, that will now be entering clinical trials to test its efficacy as a therapeutic for COVID-19.

The coalition in question is Exscalate4CoV, a public-private partnership spanning 50 partners across seven European countries (Belgium, Germany, Italy, Poland, Spain, Sweden and Switzerland). Led by Italian pharmaceutical firm Dompé, Exscalate4CoV leverages Dompé’s “exascale smart platform against pathogens” (Exscalate) and its accompanying chemical library of half a billion molecules in service of one goal: drug development for COVID-19.

Included in these 50 partners are an armada of supercomputer centers across Europe: CINECA in Italy; Barcelona Supercomputing Center (BSC) in Spain; Jülich Supercomputing Centre in Germany; and the KTH supercomputing center in Sweden. In total, the coalition claims it has access to “around 120 petaflops” of supercomputing power.

Finding raloxifene

Exscalate4CoV formed in mid-February, mere weeks before Italy was set to become the first true epicenter of the pandemic outside of China – and by early March, it had been awarded €3 million by the European Commission for COVID-19 research. As the pandemic raged across Europe, Exscalate4CoV began crunching Exscalate’s enormous molecular library.

The HPC5 system. Image courtesy of Eni.

Within a few months after that award, the consortium had tested over 400,000 molecules for their ability to dock with SARS-CoV-2’s viral proteins. This screening work was performed on four leading European supercomputers: oil and gas firm ENI’s private HPC5 system (51.7 peak petaflops); CINECA’s Marconi-100 system (29.4 peak petaflops); BSC’s MareNostrum 4 system (13.7 peak petaflops); and Jülich’s Juwels system (12 peak petaflops, soon to dramatically increase).

The raloxifene molecule.

After whittling those 400,000 molecules down to 7,000 that were tested in vitro, Exscalate4CoV identified one particularly promising preexisting pharmaceutical: raloxifene, a generic drug designed to help treat and prevent osteoporosis in postmenopausal women. Exscalate4CoV theorized that raloxifene might be able to halt the spread of the virus in mildly symptomatic COVID-19 patients by using estrogen as a defense.

“The selected drug is well-tolerated, has a well-known toxicological profile in the clinic and has shown great efficacy in in vitro experimentation,” said David Vannozzi, director of CINECA, at the time. “Now, we move on to in vivo experimentation, on animals and then on humans.”

The final test

The National Institute for Infectious Diseases in Rome.

Now, over four months later, the time for human trials has come. Exscalate4CoV has announced that, as a result of its research, AIFA (the Italian pharmaceutical regulatory agency) has greenlit a clinical trial of raloxifene. The study, based at the National Institute for Infectious Diseases in Rome and the Humanitas Research Hospital in Milan, will consist of up to 450 participants split into three treatment groups. The participants will be administered a seven-day course of either raloxifene or a placebo, after which they will be monitored for 12 weeks. Researchers will be assessing whether raloxifene safely and efficiently blocks the replication of the SARS-CoV-2 virus in human cells.

“It inhibits virus replication, thus preventing the worsening of patients with mild symptoms, and also decreases infectivity, limiting the viral load,” Marco Allegretti, head of research at Dompé, told Reuters. To that end, Dompé, the Fraunhofer Institute and the University Leuven filed a patent for the use of raloxifene in early May “in order to promote universal access to treatment,” which the consortium stressed is core to its founding principles.

Despite the promising research, Exscalate4CoV cautioned that the drug is not licensed for use in this manner outside of clinical studies as, to date, there is no conclusive evidence that raloxifene carries more benefits than risks when used with COVID-19 patients, nor is there evidence on effective dosage amounts. (In short: don’t try this at home.)

Exscalate4CoV’s ongoing research

The raloxifene research is far from the only work emerging from Exscalate4CoV. In addition to the data from its massive molecular docking initiative and over 20,000 in vitro experiments, the consortium already has ten finalized peer-reviewed articles, with ten more approaching finalization. This research, of course, is open access, with the papers available here and the data available here. Finally, the consortium is currently evaluating two additional drugs for use as COVID-19 therapeutics.

These results (and the ensuing ongoing studies) are the product of now-complete phase one of Exscalate4CoV, which aimed to identify promising molecules for those already infected with COVID-19. The second phase will aim to identify molecules capable of inhibiting future infections.

To learn more about Exscalate4CoV’s coronavirus research, listen to or read HPCwire’s interview with CINECA’s Carlo Cavazzoni, conducted at the height of Italy’s battle with COVID-19.

Subscribe to HPCwire's Weekly Update!

Be the most informed person in the room! Stay ahead of the tech trends with industry updates delivered to you every week!

HPE and NVIDIA Join Forces and Plan Conquest of Enterprise AI Frontier

June 20, 2024

The HPE Discover 2024 conference is currently in full swing, and the keynote address from Hewlett-Packard Enterprise (HPE) CEO Antonio Neri on Tuesday, June 18, was an unforgettable event. Other than being the first busi Read more…

Slide Shows Samsung May be Developing a RISC-V CPU for In-memory AI Chip

June 19, 2024

Samsung may have unintentionally revealed its intent to develop a RISC-V CPU, which a presentation slide showed may be used in an AI chip. The company plans to release an AI accelerator with heavy in-memory processing, b Read more…

ASC24 Student Cluster Competition: Who Won and Why?

June 18, 2024

As is our tradition, we’re going to take a detailed look back at the recently concluded the ASC24 Student Cluster Competition (Asia Supercomputer Community) to see not only who won the various awards, but to figure out Read more…

Qubits 2024: D-Wave’s Steady March to Quantum Success

June 18, 2024

In his opening keynote at D-Wave’s annual Qubits 2024 user meeting, being held in Boston, yesterday and today, CEO Alan Baratz again made the compelling pitch that D-Wave’s brand of analog quantum computing (quantum Read more…

Apple Using Google Cloud Infrastructure to Train and Serve AI

June 18, 2024

Apple has built a new AI infrastructure to deliver AI features introduced in its devices and is utilizing resources available in Google's cloud infrastructure.  Apple's new AI backend includes: A homegrown foun Read more…

Argonne’s Rick Stevens on Energy, AI, and a New Kind of Science

June 17, 2024

The world is currently experiencing two of the largest societal upheavals since the beginning of the Industrial Revolution. One is the rapid improvement and implementation of artificial intelligence (AI) tools, while the Read more…

HPE and NVIDIA Join Forces and Plan Conquest of Enterprise AI Frontier

June 20, 2024

The HPE Discover 2024 conference is currently in full swing, and the keynote address from Hewlett-Packard Enterprise (HPE) CEO Antonio Neri on Tuesday, June 18, Read more…

Slide Shows Samsung May be Developing a RISC-V CPU for In-memory AI Chip

June 19, 2024

Samsung may have unintentionally revealed its intent to develop a RISC-V CPU, which a presentation slide showed may be used in an AI chip. The company plans to Read more…

Qubits 2024: D-Wave’s Steady March to Quantum Success

June 18, 2024

In his opening keynote at D-Wave’s annual Qubits 2024 user meeting, being held in Boston, yesterday and today, CEO Alan Baratz again made the compelling pitch Read more…

Shutterstock_666139696

Argonne’s Rick Stevens on Energy, AI, and a New Kind of Science

June 17, 2024

The world is currently experiencing two of the largest societal upheavals since the beginning of the Industrial Revolution. One is the rapid improvement and imp Read more…

Under The Wire: Nearly HPC News (June 13, 2024)

June 13, 2024

As managing editor of the major global HPC news source, the term "news fire hose" is often mentioned. The analogy is quite correct. In any given week, there are Read more…

Labs Keep Supercomputers Alive for Ten Years as Vendors Pull Support Early

June 12, 2024

Laboratories are running supercomputers for much longer, beyond the typical lifespan, as vendors prematurely deprecate the hardware and stop providing support. Read more…

MLPerf Training 4.0 – Nvidia Still King; Power and LLM Fine Tuning Added

June 12, 2024

There are really two stories packaged in the most recent MLPerf  Training 4.0 results, released today. The first, of course, is the results. Nvidia (currently Read more…

Highlights from GlobusWorld 2024: The Conference for Reimagining Research IT

June 11, 2024

The Globus user conference, now in its 22nd year, brought together over 180 researchers, system administrators, developers, and IT leaders from 55 top research Read more…

Atos Outlines Plans to Get Acquired, and a Path Forward

May 21, 2024

Atos – via its subsidiary Eviden – is the second major supercomputer maker outside of HPE, while others have largely dropped out. The lack of integrators and Atos' financial turmoil have the HPC market worried. If Atos goes under, HPE will be the only major option for building large-scale systems. Read more…

Comparing NVIDIA A100 and NVIDIA L40S: Which GPU is Ideal for AI and Graphics-Intensive Workloads?

October 30, 2023

With long lead times for the NVIDIA H100 and A100 GPUs, many organizations are looking at the new NVIDIA L40S GPU, which it’s a new GPU optimized for AI and g Read more…

Nvidia H100: Are 550,000 GPUs Enough for This Year?

August 17, 2023

The GPU Squeeze continues to place a premium on Nvidia H100 GPUs. In a recent Financial Times article, Nvidia reports that it expects to ship 550,000 of its lat Read more…

Everyone Except Nvidia Forms Ultra Accelerator Link (UALink) Consortium

May 30, 2024

Consider the GPU. An island of SIMD greatness that makes light work of matrix math. Originally designed to rapidly paint dots on a computer monitor, it was then Read more…

Nvidia’s New Blackwell GPU Can Train AI Models with Trillions of Parameters

March 18, 2024

Nvidia's latest and fastest GPU, codenamed Blackwell, is here and will underpin the company's AI plans this year. The chip offers performance improvements from Read more…

Choosing the Right GPU for LLM Inference and Training

December 11, 2023

Accelerating the training and inference processes of deep learning models is crucial for unleashing their true potential and NVIDIA GPUs have emerged as a game- Read more…

Synopsys Eats Ansys: Does HPC Get Indigestion?

February 8, 2024

Recently, it was announced that Synopsys is buying HPC tool developer Ansys. Started in Pittsburgh, Pa., in 1970 as Swanson Analysis Systems, Inc. (SASI) by John Swanson (and eventually renamed), Ansys serves the CAE (Computer Aided Engineering)/multiphysics engineering simulation market. Read more…

Some Reasons Why Aurora Didn’t Take First Place in the Top500 List

May 15, 2024

The makers of the Aurora supercomputer, which is housed at the Argonne National Laboratory, gave some reasons why the system didn't make the top spot on the Top Read more…

Leading Solution Providers

Contributors

AMD MI3000A

How AMD May Get Across the CUDA Moat

October 5, 2023

When discussing GenAI, the term "GPU" almost always enters the conversation and the topic often moves toward performance and access. Interestingly, the word "GPU" is assumed to mean "Nvidia" products. (As an aside, the popular Nvidia hardware used in GenAI are not technically... Read more…

Intel’s Next-gen Falcon Shores Coming Out in Late 2025 

April 30, 2024

It's a long wait for customers hanging on for Intel's next-generation GPU, Falcon Shores, which will be released in late 2025.  "Then we have a rich, a very Read more…

Google Announces Sixth-generation AI Chip, a TPU Called Trillium

May 17, 2024

On Tuesday May 14th, Google announced its sixth-generation TPU (tensor processing unit) called Trillium.  The chip, essentially a TPU v6, is the company's l Read more…

The NASA Black Hole Plunge

May 7, 2024

We have all thought about it. No one has done it, but now, thanks to HPC, we see what it looks like. Hold on to your feet because NASA has released videos of wh Read more…

Nvidia Shipped 3.76 Million Data-center GPUs in 2023, According to Study

June 10, 2024

Nvidia had an explosive 2023 in data-center GPU shipments, which totaled roughly 3.76 million units, according to a study conducted by semiconductor analyst fir Read more…

Q&A with Nvidia’s Chief of DGX Systems on the DGX-GB200 Rack-scale System

March 27, 2024

Pictures of Nvidia's new flagship mega-server, the DGX GB200, on the GTC show floor got favorable reactions on social media for the sheer amount of computing po Read more…

GenAI Having Major Impact on Data Culture, Survey Says

February 21, 2024

While 2023 was the year of GenAI, the adoption rates for GenAI did not match expectations. Most organizations are continuing to invest in GenAI but are yet to Read more…

AMD Clears Up Messy GPU Roadmap, Upgrades Chips Annually

June 3, 2024

In the world of AI, there's a desperate search for an alternative to Nvidia's GPUs, and AMD is stepping up to the plate. AMD detailed its updated GPU roadmap, w Read more…

  • arrow
  • Click Here for More Headlines
  • arrow
HPCwire