Rensselaer Polytechnic Institute (RPI)

In Cell Studies, Seaweed Extract Outperforms Remdesivir in Blocking COVID-19 Virus

Heparin, a common anitcoagulent, could also form basis of a viral trap for SARS-CoV-2
24-Jul-2020 8:55 AM EDT, by Rensselaer Polytechnic Institute (RPI)

Newswise — TROY, N.Y. — In a test of antiviral effectiveness against the virus that causes COVID-19, an extract from edible seaweeds substantially outperformed remdesivir, the current standard antiviral used to combat the disease. Heparin, a common blood thinner, and a heparin variant stripped of its anticoagulant properties, performed on par with remdesivir in inhibiting SARS-CoV-2 infection in mammalian cells.

Published online today in Cell Discovery, the research is the latest example of a decoy strategy researchers from the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselear Polytechnic Institute are developing against viruses like the novel coronavirus that spawned the current global health crisis.

The spike protein on the surface of SARS-CoV-2 latches onto the ACE-2 receptor, a molecule on the surface of human cells. Once secured, the virus inserts its own genetic material into the cell, hijacking the cellular machinery to produce replica viruses. But the virus could just as easily be persuaded to lock onto a decoy molecule that offers a similar fit. The neutralized virus would be trapped and eventually degrade naturally.

Previous research has shown this decoy technique works in trapping other viruses, including dengue, Zika, and influenza A. To hear the researchers discuss their findings, watch this video.

“We’re learning how to block viral infection, and that is knowledge we are going to need if we want to rapidly confront pandemics,” said Jonathan Dordick, the lead researcher and a professor of chemical and biological engineering at Rensselaer Polytechnic Institute. “The reality is that we don’t have great antivirals. To protect ourselves against future pandemics, we are going to need an arsenal of approaches that we can quickly adapt to emerging viruses.” 

The Cell Discovery paper tests antiviral activity in three variants of heparin (heparin, trisulfated heparin, and a non-anticoagulant low molecular weight heparin) and two fucoidans (RPI-27 and RPI-28) extracted from seaweed. All five compounds are long chains of sugar molecules known as sulfated polysaccharides, a structural conformation that the results of a binding study published earlier this month in Antiviral Research suggested as an effective decoy.

The researchers performed a dose response study known as an EC50 — shorthand for the effective concentration of the compound that inhibits 50% of viral infectivity — with each of the five compounds on mammalian cells. For the results of an EC50, which are given in a molar concentration, a lower value signals a more potent compound.

RPI-27 yielded an EC50 value of approximately 83 nanomolar, while a similar previously published and independent in vitro test of remdesivir on the same mammalian cells yielded an EC50 of 770 nanomolar. Heparin yielded an EC50 of 2.1 micromolar, or about one-third as active as remdesivir, and a non-anticoagulant analog of heparin yielded an EC50 of 5.0 micromolar, about one-fifth as active as remdesivir.

A separate test found no cellular toxicity in any of the compounds, even at the highest concentrations tested.

 “What interests us is a new way of getting at infection,” said Robert Linhardt, a Rensselaer professor of chemistry and chemical biology who is collaborating with Dordick to develop the decoy strategy. “The current thinking is that the COVID-19 infection starts in the nose, and either of these substances could be the basis for a nasal spray. If you could simply treat the infection early, or even treat before you have the infection, you would have a way of blocking it before it enters the body.”

Dordick added that compounds from seaweed “could serve as a basis for an oral delivery approach to address potential gastrointestinal infection.” 

In studying SARS-CoV-2 sequencing data, Dordick and Linhardt recognized several motifs on the structure of the spike protein that promised a fit compatible with heparin, a result borne out in the binding study. The spike protein is heavily encrusted in glycans, an adaptation that protects it from human enzymes which could degrade it, and prepares it to bind with a specific receptor on the cell surface.

“It’s a very complicated mechanism that we quite frankly don’t know all the details about, but we’re getting more information,” said Dordick. “One thing that’s become clear with this study is that the larger the molecule, the better the fit. The more successful compounds are the larger sulfated polysaccharides that offer a greater number of sites on the molecules to trap the virus.” 

Molecular modeling based on the binding study revealed sites on the spike protein where the heparin was able to interact, raising the prospects for similar sulfated polysaccharides. 

“This exciting research by Professors Dordick and Linhardt is among several ongoing research efforts at CBIS, as well as elsewhere at Rensselaer, to tackle the challenges of the COVID-19 pandemic through novel therapeutic approaches and the repurposing of existing drugs,” said CBIS Director Deepak Vashishth.

Sulfated polysaccharides effectively inhibit SARS-CoV-2 in vitro” was published in Cell Discovery with the support of the National Research Foundation of Korea. At Rensselaer, Dordick and Linhardt were joined in the research by Paul S. Kwon, Seok-Joon Kwon, Weihua Jin, Fuming Zhang, and Keith Fraser, and by researchers at the Korea Research Institute of Bioscience and Biotechnology in Cheongju, Republic of Korea, and Zhejiang University of Technology in Hangzhou, China.

About Rensselaer Polytechnic Institute

Founded in 1824, Rensselaer Polytechnic Institute is America’s first technological research university. Rensselaer encompasses five schools, 32 research centers, more than 145 academic programs, and a dynamic community made up of more than 7,900 students and over 100,000 living alumni. Rensselaer faculty and alumni include more than 145 National Academy members, six members of the National Inventors Hall of Fame, six National Medal of Technology winners, five National Medal of Science winners, and a Nobel Prize winner in Physics. With nearly 200 years of experience advancing scientific and technological knowledge, Rensselaer remains focused on addressing global challenges with a spirit of ingenuity and collaboration. To learn more, please visit www.rpi.edu.

SEE ORIGINAL STUDY




Filters close

Showing results

110 of 2878
Released: 12-Aug-2020 9:15 AM EDT
Mount Sinai’s Arnhold Institute for Global Health Partners with NYC Health + Hospitals on COVID-19 Unit for Research at Elmhurst (CURE-19)
Mount Sinai Health System

Collaboration Brings Together Clinicians and Researchers on the Front Lines of COVID-19 to Support Innovative Solutions for Health Disparities

Newswise: 239806_web.jpg
Released: 12-Aug-2020 9:00 AM EDT
Malaria discovery could expedite antiviral treatment for COVID-19
Royal Melbourne Institute of Technology (RMIT) University

The study, conducted by an international team and led by RMIT University's Professor Christian Doerig, outlines a strategy that could save years of drug discovery research and millions of dollars in drug development by repurposing existing treatments designed for other diseases such as cancer.

Released: 12-Aug-2020 9:00 AM EDT
Researchers show mathematically how to best reopen your business after lockdown
Frontiers

In the USA, where the curve of infections has not yet flattened since the beginning of the pandemic, 158,000 people have died from Covid-19 already.

Newswise: How Cedars-Sinai Predicts Number of COVID-19 Patients
Released: 12-Aug-2020 9:00 AM EDT
How Cedars-Sinai Predicts Number of COVID-19 Patients
Cedars-Sinai

When the novel coronavirus started spreading across the U.S., hospital leaders were faced with a unique challenge: How could they accurately forecast the number of patients who would need hospitalization when no one knew what to expect from this new disease? To answer this and other questions, the data science team at Cedars-Sinai developed a machine learning platform to predict staffing needs. The team adjusted the platform's algorithms to forecast data points related to the novel coronavirus. Now the platform tracks local hospitalization volumes and the rate of confirmed COVID-19 cases, running multiple forecasting models to help anticipate and prepare for increasing COVID-19 patient volumes with an 85%-95% degree of accuracy.

Released: 12-Aug-2020 5:05 AM EDT
USC Center for the Digital Future study finds huge gaps in views based on political beliefs on alternatives to traditional voting; half want changes in political conventions
USC Annenberg School for Communication and Journalism

A majority of Americans say national elections need to change because of the COVID-19 pandemic, including broad support for voting by mail and online political conventions, reports a new study by the USC Center for the Digital Future.

access_time Embargo lifts in 2 days
Embargo will expire: 12-Aug-2020 6:00 PM EDT Released to reporters: 11-Aug-2020 11:00 PM EDT

A reporter's PressPass is required to access this story until the embargo expires on 12-Aug-2020 6:00 PM EDT The Newswise PressPass gives verified journalists access to embargoed stories. Please log in to complete a presspass application. If you have not yet registered, please Register. When you fill out the registration form, please identify yourself as a reporter in order to advance to the presspass application form.

Released: 11-Aug-2020 6:50 PM EDT
Untapped potential for TikTok to convey COVID-19 guidance
De Gruyter

Research published in DeGruyter's International Journal of Adolescent Medicine and Health suggests TikTok is rich with untapped educational potential.

Released: 11-Aug-2020 5:40 PM EDT
Experimental COVID-19 vaccine prevents severe disease in mice
Washington University in St. Louis

Researchers at Washington University School of Medicine in St. Louis have created a COVID-19 vaccine candidate from a replicating virus. This experimental vaccine has proven effective at preventing pneumonia in mice.


Showing results

110 of 2878

close
1.07559