Seaweed extract is superior to lemdecivir in suppression of SARS-CoV-2 in cell studies

Reviewed by Emily Henderson, B.Sc.July 24, 2020

In tests of antiviral efficacy against the virus that causes COVID-19, extracts from edible seaweed significantly exceeded lemdesibir, the current standard antiviral drug used to fight disease. Heparin, which is a general anticoagulant, and heparin mutants with its anticoagulant action removed, in the same manner as lemdecivir in suppressing SARS-CoV-2 infection in mammalian cells.

Published online today Cell discoveryThis study is the latest development being developed by decoy strategy researchers at the Rensselear Polytechnic Institute’s Center for Biotechnology and Interdisciplinary Research (CBIS) against viruses such as the new coronavirus that have caused the current global health crisis. Is an example.

A surface spike protein on SARS-CoV-2 latches to the ACE-2 receptor, a molecule on the surface of human cells. Once secured, the virus inserts its genetic material into the cell and hijacks the cellular machinery to produce a replicating virus. However, the virus can be easily persuaded to lock onto a decoy molecule that provides a similar fit. The neutralized virus is trapped and eventually spontaneously degraded.

Previous studies have shown that this decoy technique is effective in trapping other viruses such as Dengue, Zika, and influenza A. Watch this video to discuss what the researchers have discovered.

We’re learning how to stop viral infections, and that’s the knowledge we’ll need if we try to quickly confront a pandemic. In reality, there are no good antiviral drugs. To protect yourself from future pandemics, you need a set of approaches that can quickly adapt to new viruses. “

Jonathan Doldick, Principal Investigator and Professor of Chemical and Biotechnology at the Rensselaer Polytechnic Institute

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

The researchers conducted a dose-response study for each of the five compounds on mammalian cells, known as the EC50 (abbreviation for effective concentration of compound that inhibits 50% of viral infectivity). EC50 results, given in molarity, indicate that the lower the value, the more potent the compound.

While the EC50 value for RPI-27 was approximately 83 nanomolar, a similar previously published independent in vitro study of lemdecibir on the same mammalian cell yielded an EC50 of 770 nanomolar. Heparin showed an EC50 of 2.1 micromolar, or about one-third the activity of lemdecibir, and the non-anticoagulant analog of heparin showed an EC50 of 5.0 micromolar, about one-fifth the activity of lemdecibir. It was

In another test, none of the compounds were cytotoxic at the highest concentrations tested.

“We’re interested in new ways to deal with infections,” said Robert L., a professor of chemistry and chemical biology at Rensselaer who is working with Doldick to develop a decoy strategy. Rinhart said. “The current idea is that COVID-19 infections start in the nose and either of these substances could be the basis for nasal drops. If treated early or before infection, There is a way to block it before it enters the body.”

Dodick added that compounds from seaweed “may serve as the basis for an oral delivery approach to combating potential gastrointestinal infections.”

In a study of SARS-CoV-2 sequence data, Dordick and Linhardt recognized several structural motifs in spike proteins that promise heparin compatibility. Spike proteins are strongly covered by glycans. Glycans protect them from human enzymes that can degrade them and prepare them to bind to specific cell surface receptors.

“It’s a very complex mechanism and, frankly, we don’t know all the details, but we have more information,” Doldick said. “One of the findings in this study is that the larger the molecule, the more compatible it is. The more successful compounds are the larger sulfates that provide more sites on the molecule for trapping the virus. It is a chemical polysaccharide.”

Molecular modeling based on binding studies has revealed sites on spike proteins with which heparin can interact, increasing the likelihood of similar sulfated polysaccharides.

“This exciting study by Professors Doldick and Lynnhardt presents several ongoing projects elsewhere in CBIS and Rensselaer to address the challenges of the COVID-19 pandemic through new therapeutic approaches and diversion of existing drugs. It’s one of my research activities,” said CBIS Director Deepak Vasisht.

“Sulfated polysaccharides effectively inhibit SARS-CoV-2 in vitro” published Cell discovery With the support of the Korean National Research Foundation. In Rensselaer, Doddick and Linhart participated in the study by Paul S. Kwong, Sok Jun Kwong, Weifazin, Humming Chan, Keith Fraser, and researchers from the Korean Institute of Bioscience and Biotechnology in Cheongju, South Korea. Zhejiang Institute of Technology in Hangzhou.