Massachusetts Startup Uses Supercomputing to Identify Four Promising COVID Therapeutics

By Oliver Peckham

April 26, 2021

Amid rising global cases and threatening variants, a major gap remains to be filled in the world’s strategy for defeating the pandemic: effective therapeutics. Now, a Massachusetts startup powered by a wide range of HPC resources – including hometown resources from the Massachusetts Green High Performance Computing Center (MGHPCC) – has identified four promising FDA-approved drugs whose efficacy as COVID-19 therapeutics is supported by data from millions of patients.

“We developed our own simulation suite,” explained Joy Alamgir, founder of the startup in question, called ARIScience, in an interview with HPCwire. “That was the genesis of ARIScience, where we wanted a novel way to look at compounds – particularly, compounds that we want to interrupt – and a way to put in quantum observations along with classical simulation on the ligand side. … And we purposely wanted to do it homogeneously and on the same development stack, which allows us to effectively maintain it and also allows us to avoid any installation heartache that we may have as we use different kinds of compute resources that are available to us.”

A couple years in, of course, the landscape changed somewhat. “Once COVID hit the U.S. back around April of last year,” Alamgir said, “we redirected our efforts to see if there was an existing compound from all the FDA-approved drugs that we could use our simulation platform with to see if there were specific coronavirus proteins that we could interrupt.”

Alamgir wanted to simulate the structures of 1,513 FDA-approved drugs, then conduct a free energy analysis against 11 key SARS-CoV-2 proteins to see which of those drug molecules showed the best potential for disrupting those proteins. 

Initially, Alamgir worked with ARIScience’s in-house HPC cluster – a small set of “essentially three nodes” equipped with Intel CPUs dating back a couple generations of hardware. 

“Our internal HPC very quickly ran out of computing power,” Alamgir said, “at which point we reached out to [John Goodhue, executive director of the] MGHPCC and a few other organizations to see if they could allow us to run it on their HPC platforms.” Beyond the MGHPCC, Alamgir received allocations at the Pittsburgh Supercomputing Center (PSC), the Texas Advanced Computing Center (TACC) and the Universities of Maine and North Dakota. 

Triamcinolone (red) interacting with the NSP1 protein on SARS-CoV-2. Image courtesy of Joy Alamgir.

None of the allocations were massive, and Alamgir took advantage of the flexibility of ARIScience’s platform to spread the load across the systems using Slurm. On each system, he ballparked, the project was using somewhere between six and 30 nodes at a time, with each simulation job taking a few hours and all 1,513 analyses for one protein taking several days to complete.

At the end of all that simulating, Alamgir was left with 18 promising FDA-approved drugs.

“At which point we were like, okay, great, we have these 18 results,” he said. “What do we do with them, right? It’s not like we can run 18 clinical trials.”

So Alamgir decided to take the analysis one step further and vet the results against real patient data. After “a lot of requesting,” ARIScience was granted access to data from the National COVID Cohort Collaborative (N3C) data from the National Institutes of Health (NIH), making the company one of the first commercial entities to gain access to the massive dataset, which contains detailed – and yes, deidentified – data from 1.5 million patients. 

Carefully controlling for demographic data that might affect the results, Alamgir then used a “very sophisticated statistical analysis” to examine the real-world differences in mortality between patients who used one of those 18 drugs and patients who didn’t. 

The result: four drugs (amoxicillin, metformin, hydrochlorothiazide and triamcinolone) that were each “statistically significantly associated with reduced COVID mortality of about 25 percent.” Furthermore – although the sample size was lower and the data analysis remains ongoing – Alamgir shared that the combination effect of hydrochlorothiazide and metformin appeared to be even stronger. “The mortality rate reduction was the highest for the patients that were taking both of them,” he said. “We detected a 41 percent reduction in COVID mortality odds.” (The other combination effects had not yet been similarly assessed.)

For now, Alamgir’s analysis is constrained to mortality – the most crucial outcome – and further patient data may be a bit more difficult to work with. “We purposefully froze our analysis using a data release of about mid-December of 2020,” he said. “The reason primarily is that starting in late December, the vaccination campaigns in the U.S. have started and depending on who got vaccinated or not, you introduce additional unknowns into this statistical analysis.”

So now, Alamgir and ARIScience are running with what they have: highly promising results for four FDA-approved drugs. With vaccines taking hold in the U.S. and critical peaks occurring elsewhere around the world, the company is turning its attention to South America and South Asia to explore the possibility of a randomized clinical trial to further bolster the drugs’ efficacy in staving off COVID mortality.

For Goodhue and the MGHPCC, this is a familiar success story, with the director characterizing the partnership between the MGHPCC and ARIScience as one of the center’s many actions “at the trailing edge of research and the leading edge of societal impact.” The center’s previous accounts, he said, included the founders of Moderna and a range of successful startups. “All of them started with us when they were early-stage,” he said. “If I was trying to impress people, I’d say we’ve managed to help a couple of companies on their way to their exits by acquisition, I think yielding a total of three quarters of a billion dollars.”

During the pandemic, the MGHPCC has been running what Goodhue explains as a “mini version” of the COVID-19 HPC Consortium, offering computing resources to companies based in Massachusetts with research ideas for tackling the virus. Right now, Goodhue said, the center is actively partnered with around a half dozen companies.

Subscribe to HPCwire's Weekly Update!

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

IBM Research Debuts 2nm Test Chip with 50 Billion Transistors

May 6, 2021

IBM Research today announced the successful prototyping of the world's first 2 nanometer chip, fabricated with silicon nanosheet technology on a standard 300mm bulk wafer. With ~50 billion transistors, the chip will enab Read more…

Supercomputer-Powered CRISPR Simulation Lights Path to Better DNA Editing

May 5, 2021

CRISPR-Cas9 – mostly just known as CRISPR – is a powerful genome editing tool that uses an enzyme (Cas9) to slice off sections of DNA and a guide RNA to repair and modify the DNA as desired, opening the door for cure Read more…

LRZ Announces New Phase of SuperMUC-NG Supercomputer with Intel’s ‘Ponte Vecchio’ GPU

May 5, 2021

At the Leibniz Supercomputing Centre (LRZ) in München, Germany – one of the constituent centers of the Gauss Centre for Supercomputing (GCS) – the SuperMUC-NG system has stood tall for several years, placing 15th on Read more…

HPC Simulations Show How Antibodies Quash SARS-CoV-2

May 5, 2021

Following more than a year of rapid-fire research and pharmaceutical development, nearly a billion COVID-19 vaccine doses have been administered around the world, with many of those vaccines proving remarkably effective Read more…

Crystal Ball Gazing at Nvidia: R&D Chief Bill Dally Talks Targets and Approach

May 4, 2021

There’s no quibbling with Nvidia’s success. Entrenched atop the GPU market, Nvidia has ridden its own inventiveness and growing demand for accelerated computing to meet the needs of HPC and AI. Recently it embarked on an ambitious expansion by acquiring Mellanox (interconnect)... Read more…

AWS Solution Channel

FLYING WHALES runs CFD workloads 15 times faster on AWS

FLYING WHALES is a French startup that is developing a 60-ton payload cargo airship for the heavy lift and outsize cargo market. The project was born out of France’s ambition to provide efficient, environmentally friendly transportation for collecting wood in remote areas. Read more…

2021 Winter Classic – Coaches Chat

May 4, 2021

The Winter Classic Invitational Student Cluster Competition raged for all last week and now we’re into the week of judging interviews. Time has been flying. So as we wait for results, let’s dive a bit deeper into t Read more…

IBM Research Debuts 2nm Test Chip with 50 Billion Transistors

May 6, 2021

IBM Research today announced the successful prototyping of the world's first 2 nanometer chip, fabricated with silicon nanosheet technology on a standard 300mm Read more…

LRZ Announces New Phase of SuperMUC-NG Supercomputer with Intel’s ‘Ponte Vecchio’ GPU

May 5, 2021

At the Leibniz Supercomputing Centre (LRZ) in München, Germany – one of the constituent centers of the Gauss Centre for Supercomputing (GCS) – the SuperMUC Read more…

Crystal Ball Gazing at Nvidia: R&D Chief Bill Dally Talks Targets and Approach

May 4, 2021

There’s no quibbling with Nvidia’s success. Entrenched atop the GPU market, Nvidia has ridden its own inventiveness and growing demand for accelerated computing to meet the needs of HPC and AI. Recently it embarked on an ambitious expansion by acquiring Mellanox (interconnect)... Read more…

Intel Invests $3.5 Billion in New Mexico Fab to Focus on Foveros Packaging Technology

May 3, 2021

Intel announced it is investing $3.5 billion in its Rio Rancho, New Mexico, facility to support its advanced 3D manufacturing and packaging technology, Foveros. Read more…

Supercomputer Research Shows Standard Model May Withstand Muon Discrepancy

May 3, 2021

Big news recently struck the physics world: researchers at the Fermi National Accelerator Laboratory (FNAL), in the midst of their Muon g-2 experiment, publishe Read more…

NWChemEx: Computational Chemistry Code for the Exascale Era

April 29, 2021

A team working on biofuel research is rewriting the decades-old NWChem software program for the exascale era. The new software, NWChemEx, will enable computatio Read more…

HPE Will Build Singapore’s New National Supercomputer

April 28, 2021

More than two years ago, Singapore’s National Supercomputing Centre (NSCC) announced a $200 million SGD (~$151 million USD) investment to boost its supercomputing power by an order of magnitude. Today, those plans come closer to fruition with the announcement that Hewlett Packard Enterprise (HPE) has been awarded... Read more…

Arm Details Neoverse V1, N2 Platforms with New Mesh Interconnect, Advances Partner Ecosystem

April 27, 2021

Chip designer Arm Holdings is sharing details about its Neoverse V1 and N2 cores, introducing its new CMN-700 interconnect, and showcasing its partners' plans t Read more…

Julia Update: Adoption Keeps Climbing; Is It a Python Challenger?

January 13, 2021

The rapid adoption of Julia, the open source, high level programing language with roots at MIT, shows no sign of slowing according to data from Julialang.org. I Read more…

Intel Launches 10nm ‘Ice Lake’ Datacenter CPU with Up to 40 Cores

April 6, 2021

The wait is over. Today Intel officially launched its 10nm datacenter CPU, the third-generation Intel Xeon Scalable processor, codenamed Ice Lake. With up to 40 Read more…

CERN Is Betting Big on Exascale

April 1, 2021

The European Organization for Nuclear Research (CERN) involves 23 countries, 15,000 researchers, billions of dollars a year, and the biggest machine in the worl Read more…

HPE Launches Storage Line Loaded with IBM’s Spectrum Scale File System

April 6, 2021

HPE today launched a new family of storage solutions bundled with IBM’s Spectrum Scale Erasure Code Edition parallel file system (description below) and featu Read more…

10nm, 7nm, 5nm…. Should the Chip Nanometer Metric Be Replaced?

June 1, 2020

The biggest cool factor in server chips is the nanometer. AMD beating Intel to a CPU built on a 7nm process node* – with 5nm and 3nm on the way – has been i Read more…

Saudi Aramco Unveils Dammam 7, Its New Top Ten Supercomputer

January 21, 2021

By revenue, oil and gas giant Saudi Aramco is one of the largest companies in the world, and it has historically employed commensurate amounts of supercomputing Read more…

Quantum Computer Start-up IonQ Plans IPO via SPAC

March 8, 2021

IonQ, a Maryland-based quantum computing start-up working with ion trap technology, plans to go public via a Special Purpose Acquisition Company (SPAC) merger a Read more…

Can Deep Learning Replace Numerical Weather Prediction?

March 3, 2021

Numerical weather prediction (NWP) is a mainstay of supercomputing. Some of the first applications of the first supercomputers dealt with climate modeling, and Read more…

Leading Solution Providers

Contributors

Livermore’s El Capitan Supercomputer to Debut HPE ‘Rabbit’ Near Node Local Storage

February 18, 2021

A near node local storage innovation called Rabbit factored heavily into Lawrence Livermore National Laboratory’s decision to select Cray’s proposal for its CORAL-2 machine, the lab’s first exascale-class supercomputer, El Capitan. Details of this new storage technology were revealed... Read more…

AMD Launches Epyc ‘Milan’ with 19 SKUs for HPC, Enterprise and Hyperscale

March 15, 2021

At a virtual launch event held today (Monday), AMD revealed its third-generation Epyc “Milan” CPU lineup: a set of 19 SKUs -- including the flagship 64-core, 280-watt 7763 part --  aimed at HPC, enterprise and cloud workloads. Notably, the third-gen Epyc Milan chips achieve 19 percent... Read more…

African Supercomputing Center Inaugurates ‘Toubkal,’ Most Powerful Supercomputer on the Continent

February 25, 2021

Historically, Africa hasn’t exactly been synonymous with supercomputing. There are only a handful of supercomputers on the continent, with few ranking on the Read more…

New Deep Learning Algorithm Solves Rubik’s Cube

July 25, 2018

Solving (and attempting to solve) Rubik’s Cube has delighted millions of puzzle lovers since 1974 when the cube was invented by Hungarian sculptor and archite Read more…

GTC21: Nvidia Launches cuQuantum; Dips a Toe in Quantum Computing

April 13, 2021

Yesterday Nvidia officially dipped a toe into quantum computing with the launch of cuQuantum SDK, a development platform for simulating quantum circuits on GPU-accelerated systems. As Nvidia CEO Jensen Huang emphasized in his keynote, Nvidia doesn’t plan to build... Read more…

The History of Supercomputing vs. COVID-19

March 9, 2021

The COVID-19 pandemic poses a greater challenge to the high-performance computing community than any before. HPCwire's coverage of the supercomputing response t Read more…

HPE Names Justin Hotard New HPC Chief as Pete Ungaro Departs

March 2, 2021

HPE CEO Antonio Neri announced today (March 2, 2021) the appointment of Justin Hotard as general manager of HPC, mission critical solutions and labs, effective Read more…

Microsoft to Provide World’s Most Powerful Weather & Climate Supercomputer for UK’s Met Office

April 22, 2021

More than 14 months ago, the UK government announced plans to invest £1.2 billion ($1.56 billion) into weather and climate supercomputing, including procuremen Read more…

  • arrow
  • Click Here for More Headlines
  • arrow
HPCwire