A New Way to Fight Pandemics: Use Decoys to Trap the Viruses that Cause Them

With a vaccine for SARS-CoV-2 still months into the future, it’s clear that we need better antivirals to hold COVID-19 and future pandemics at bay. One strategy uses a decoy to block viruses at the point where they latch onto human cells, stopping infection before it can begin.

To infect a cell, a virus must first latch onto a specific target on the cell surface, slice through the cell membrane, and insert its own genetic instructions, hijacking the cellular machinery within to produce replicas of the virus. But the virus could just as easily be persuaded to lock onto a decoy molecule, provided that molecule offers the same fit as the cellular target. Once bound to a decoy, the virus would be neutralized, unable to infect a cell or free itself, and would eventually degrade.

This decoy strategy has shown promise in combating a number of viruses, including SARS-CoV-2, dengue, Zika, and influenza A.

Two prominent researchers at Rensselaer Polytechnic Institute — Jonathan Dordick, a chemical engineer, and Robert Linhardt, internationally recognized for his creation of synthetic heparin — focus on viruses that use glycoproteins to latch onto human cells, a trait common to many viruses including coronaviruses. Their work studies how viruses gain entry into human cells at the molecular level and identifies safe, effective compounds to offer as a decoy.

In their most recent test of this viral decoy strategy on mammalian cells, Dordick and Linhardt demonstrated that a compound derived from edible seaweeds substantially outperforms remdesivir, the current standard antiviral used to combat COVID-19. 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. Both compounds bind tightly to the spike protein on the surface of SARS-CoV-2, the same strategy the team employed in their previous viral work.

In 2019, the team created a trap for dengue virus, attaching specific aptamers — molecules the viral latches will bind to — precisely to the tips and vertices of a five-pointed star made of folded DNA. Floating in the bloodstream, the trap lights up when sprung, creating the world’s most sensitive test for mosquito-borne diseases.

Dordick and Linhardt are available to speak on the viral decoy strategy, similar antiviral research efforts, and the need for more effective antivirals in future pandemic control.