University of California San Diego

Supercomputers Help Model Potential SARS-CoV2 Protease Inhibitors for COVID-19

Computational Docking Illustrates Possibilities for Repurposing FDA-Approved Drugs

By Kimberly Mann Bruch, SDSC Communications

Newswise — A team of San Diego Supercomputer Center (SDSC) researchers recently created a pharmacophore model and conducted data mining of the database of drugs approved by the U.S. Federal Drug Administration (FDA) to find potential inhibitors of papain-like protease of SARS-CoV2, one of the main viral proteins responsible for COVID-19.

The study, recently published in PeerJ, found that among the drugs computationally selected were those currently used to inhibit HIV, Hepatitis C, and cytomesalovirus (CMV) as well as a set of drugs that have recently demonstrated positive effects on combatting COVID-19.

The SDSC team included Igor Tsigelny, a researcher in structural biology, molecular modeling, and bioinformatics; Valentina Kouznetsova, who has expertise in protein modeling, metabolomics, biomarkers of diseases, and cancer diagnostics; Mark Miller (bioinformatics, phylogenetics eukaryotic cell biology, and metabolic engineering); and Mahidhar Tatineni, SDSC’s User Support Group Lead and a programmer analyst for high-performance computing. Tsigelny is also affiliated with the UC San Diego Moores Cancer Center.

SDSC’s Comet supercomputer was used for the computational docking of the selected drugs, covering a combined 4.3 million docking poses. After careful analysis, the researchers determined the most optimal compounds for simulated docking, which refers to the way drugs bind to papain-like protease.

“Once we completed the docking computations, we discovered that only some drugs had seemingly the best docking energies to bind viral protein that can help to fight COVID-19,” said Kouznetsova.

According to Tsigelny, some of the drugs selected by the pharmacophore search are already being experimentally tested for other viruses. He noted that that 11 compounds have been shown to be effective in treating other viruses - amodiaquine, chloroquine, sorafenib, dasatenib, hydroxychloroquine, bortezomib, topotecan, manidipine, lovastatin, cefitinib, and ritonavir.

Earlier this year, Kouznetsova and Tsigelny created a similar pharmacophore model that involved the data mining of the conformational database of FDA-approved drugs. With this earlier model, they identified 64 compounds as potential inhibitors of another SARS-CoV2 viral protein: main protease, also one of the main proteins responsible for COVID-19. Among the compounds selected then were two HIV protease inhibitors, two hepatitis C protease inhibitors, and three drugs that have already shown positive results in testing with COVID-19. Details of that study can be found here.

Support for this research included the San Diego Supercomputer Center. Comet is funded by the National Science Foundation (ACI #1341698). Mark Miller was supported by National Institutes of Health (R01 GM126463). Other authors received no funding for this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

About SDSC

The San Diego Supercomputer Center (SDSC) is a leader and pioneer in high-performance and data-intensive computing, providing cyberinfrastructure resources, services, and expertise to the national research community, academia, and industry. Located on the UC San Diego campus, SDSC supports hundreds of multidisciplinary programs spanning a wide variety of domains, from astrophysics and earth sciences to disease research and drug discovery. In late 2020 SDSC will launch its newest National Science Foundation-funded supercomputer, Expanse. At over twice the performance of CometExpanse supports SDSC’s theme of ‘Computing without Boundaries’ with a data-centric architecture, public cloud integration, and state-of-the art GPUs for incorporating experimental facilities and edge computing.

 

SEE ORIGINAL STUDY




Filters close

Showing results

110 of 4573
Released: 15-Jan-2021 5:40 PM EST
Research Links Social Isolation to COVID-19 Protocol Resistance
Humboldt State University

As health officials continue to implore the public to wear masks and practice social distancing, recent research by Humboldt State University Psychology Professor Amber Gaffney provides key insights into connections between social isolation, conspiratorial thinking, and resistance to COVID-19 protocols.

Newswise: Rapid blood test identifies COVID-19 patients at high risk of severe disease
Released: 15-Jan-2021 5:35 PM EST
Rapid blood test identifies COVID-19 patients at high risk of severe disease
Washington University in St. Louis

Scientists at Washington University School of Medicine in St. Louis have shown that a relatively simple and rapid blood test can predict which patients with COVID-19 are at highest risk of severe complications or death. The blood test measures levels of mitochondrial DNA, which normally resides inside the energy factories of cells. Mitochondrial DNA spilling out of cells and into the bloodstream is a sign that a particular type of violent cell death is taking place in the body.

Released: 15-Jan-2021 2:55 PM EST
COVID-19 deaths really are different. But best practices for ICU care should still apply, studies suggest.
Michigan Medicine - University of Michigan

COVID-19 deaths are indeed different from other lung failure deaths, according to two recent studies, with 56% of COVID-19 patients dying primarily from the lung damage caused by the virus, compared with 22% of those whose lungs fail due to other causes. But, the researchers conclude, the kind of care needed to help sustain people through the worst cases of all forms of lung failure is highly similar, and just needs to be fine-tuned.

Released: 15-Jan-2021 2:50 PM EST
45% of adults over 65 lack online medical accounts that could help them sign up for COVID-19 vaccinations
Michigan Medicine - University of Michigan

As the vaccination of older adults against COVID-19 begins across the country, new poll data suggests that many of them don’t yet have access to the “patient portal” online systems that could make it much easier for them to schedule a vaccination appointment. In all, 45% of adults aged 65 to 80 had not set up an account with their health provider’s portal system.

Released: 15-Jan-2021 1:30 PM EST
New England Journal of Medicine publishes COVID-19 treatment trial results
University of Texas at San Antonio

A clinical trial involving COVID-19 patients hospitalized at UT Health San Antonio and University Health, among roughly 100 sites globally, found that a combination of the drugs baricitinib and remdesivir reduced time to recovery, according to results published Dec. 11 in the New England Journal of Medicine.

Released: 15-Jan-2021 12:40 PM EST
DNA test can quickly identify pneumonia in patients with severe COVID-19, aiding faster treatment
University of Cambridge

Researchers have developed a DNA test to quickly identify secondary infections in COVID-19 patients, who have double the risk of developing pneumonia while on ventilation than non-COVID-19 patients.

Released: 15-Jan-2021 12:30 PM EST
Fight CRC To Present Research Findings on The Impact of COVID-19 on the Colorectal Cancer Community at 2021 GI ASCO
Fight Colorectal Cancer

Fight Colorectal Cancer presents abstract at Gastrointestinal Cancer Symposium highlighting the need to address the barriers and opportunities for care within the colorectal cancer community during the COVID-19 pandemic

Released: 15-Jan-2021 12:25 PM EST
Technion to Award Honorary Doctorate to Pfizer CEO Dr. Albert Bourla
American Technion Society

Israel's Technion will award an honorary doctorate to Pfizer CEO and Chairman Dr. Albert Bourla, for leading the development of the novel vaccine against SARS-CoV-2, the virus that causes COVID-19. The honorary doctorate will be conferred at the Technion Board of Governors meeting in November 2021.

Released: 15-Jan-2021 11:30 AM EST
UW researchers develop tool to equitably distribute limited vaccines
University of Wisconsin-Madison

Researchers at the University of Wisconsin School of Medicine and Public Health and UW Health have developed a tool that incorporates a person’s age and socioeconomic status to prioritize vaccine distribution among people who otherwise share similar risks due to their jobs.


Showing results

110 of 4573

close
4.59324