Paolo Rossi Castelli 29 July 2021 6 min read

A means of ending Covid with defective copies of the virus?

Cutting-edge research from Pennsylvania University. When duplicated, viruses also create “flawed” copies of their genetic code. Once modified, these copies might actually be used as a treatment against Covid.

For the moment it is merely what scientists call a proof of concept, a demonstration that a hypothesis is correct based on a certain kind of experiment.

But if the results of subsequent stages prove researchers at Pennsylvania State University right, the fight against the SARS-CoV-2 virus which causes Covid-19 might explore new horizons.

What is it about?

Geneticists and virologists in the US have been conducting a series of in vitro tests to see just how plausible it would be to turn coronavirus against itself by harnessing some of its innate natural characteristics, and its defects, to neutralise it; and early results look promising.

Let’s take a closer look at how this method works, or could work. As the researchers in science magazine PeerJ explained, all viruses, when replicating inside the host, also produce defective copies of themselves with large deletions or mistakes in the genome. These defective copies of the virus are called defective interfering viruses (DI).

The DI viruses, namely the defective copies, are often not eliminated (one might be tempted to say that “they do not die”, although this is not quite the correct term). Instead, they engage in a battle with the “regular” viruses because they, too, want to live and replicate. In this battle for survival inside the cells, it is often the DI viruses that win out, because they have a genetic code which is shorter and therefore duplicates more quickly, and because they can “steal” some of the parts of genetic code they are missing from regular viruses, parts which are vital to complete replication, by hijacking them.

“Antagonists” constructed in the lab

Researchers at Pennsylvania University decided to exploit this competition by using genetic engineering techniques to create a series of highly parasitic DI copies of coronavirus. In the laboratory, they introduced them into cells (taken from monkeys) which had already been infected with ordinary SARS-CoV-2.

They observed that in a very short space of time, the DI viruses caused a sharp drop in the concentration of normal viruses (halving the amounts in just 24 hours), because the speed of replication was two-fold that of “regular” SARS-CoV-2.

Moreover, the quantity of genetic material of the DI viruses increased 3.3 times faster than the original. This is a positive aspect given that unlike the original ones, the DI viruses created by the American researchers do not cause Covid.

New studies underway

According to the experts, this data is as yet insufficient to be able to view therapy with DI viruses as a fully-fledged treatment, but experiments will now continue.

Attempts will also be made to understand what happens over the course of time, because the competition phenomenon does not grow in a linear way: the more the normal genetic material decreases, because it is used by the DI viruses, the more the replication efficiency of the DI viruses themselves also drops as they no longer have the molecules they can exploit. In the long run, this puts an end to the replication of all the virus types.

It will also be necessary to understand what system to use to carry the DI copies into the cells. And, of course, the topic of virus variants will also need to be tackled. So, there is still a great deal of work to be done, but the approach seems to be an interesting one, and offers a new means of fighting this and other types of viruses.


Paolo Rossi Castelli

Journalist since 1983, Paolo has been dealing with scientific divulgation for years, especially in the fields of medicine and biology. He is the creator of Sportello Cancro, the site created by on oncology in collaboration with the Umberto Veronesi Foundation. He collaborated with the pages of the Science of Corriere della Sera for several years. He is the founder and director of PRC-Comunicare la scienza.