The plant-based antiviral agent thapsigargin (TG), derived from a group of poisonous plants known as 'deadly carrots', appears to be effective against all variants of SARS-CoV-2 in the lab – and that includes the quick-spreading Delta variant.
A previous study published in February demonstrated that TG can be effective against a host of viruses. Now, this latest work by the same research team confirms that the antiviral also isn't being outflanked as SARS-CoV-2 evolves. With the emergence of new variants an ongoing possibility, it's intriguing to observe the continuous efficacy of TG.
In tests on cell cultures in the lab, doses of TG delivered either before infection or during active infection were shown to block and inhibit SARS-CoV-2 variants, triggering a broad and powerful protective response.
"A single pre-infection priming dose of TG effectively blocked all single-variant infections and every combination (AB, AD, BD variants) of co-infection at greater than 95 percent relative to controls," write the researchers in their published paper.
As a host-centric antiviral, TG seems to break some of the mechanisms that viruses like SARS-CoV-2 hijack in host cells to replicate themselves and spread throughout the body.
"All available data (generated by us and others) as exemplified in influenza virus, respiratory syncytial virus, and coronaviruses, including SARS-CoV-2, indicate that TG does not prevent viral entry but rather triggers intracellular pathways to inhibit virus replication," the team writes.
The cell culture study also confirmed the higher replication rate and cell-to-cell transmission rate of the Delta variant: it was found to spread at four times the rate of the Alpha variant of coronavirus and at nine times the rate of the Beta variant.
What's more, Delta can accelerate the multiplication of other variants when co-infections occur. If someone succumbs to two variants of SARS-CoV-2 at the same time, then Delta acts as an extra boost for whatever other variant it's partnering up with.
"Our new study has given us better insights into the dominance of the Delta variant," says Kin-Chow Chang, a professor of Veterinary Molecular Medicine at the University of Nottingham in the UK.
"Even though we have shown that this variant is clearly the most infectious and promotes production of other variants in co-infections, we are pleased to have shown that TG is just as effective against all of them."
While vaccinations massively reduce the risk of getting infected with SARS-CoV-2, they don't reduce the risk entirely – and of course, there are substantial numbers of people who can't or won't agree to get a jab to protect themselves against the virus.
With that in mind, finding new treatments to manage COVID-19 will remain a high priority for controlling the ongoing global pandemic. It's not certain that TG would be as effective against future variants, but the signs are good.
After demonstrating its efficacy in the lab, the next step is actually developing treatments from TG, which would of course take time – as you might expect from an agent developed from a poisonous plant, it's going to take a significant amount of further research to turn it into something safe for humans.
Testing it against cell cultures and getting promising results is by no means even a guarantee that this antiviral would eventually pass a clinical trial, but it's a hugely exciting first step for sure.
"Together, these results point to the antiviral potential of TG as a post-exposure prophylactic and an active therapeutic agent," says Kin-Chow Chang.
The research has been published in Virulence.