’Deadly carrot' compound may be effective against SARS-CoV-2

• A new study investigates how SARS-CoV-2 behaves when two variants of the virus coinfect human cells.
• The researchers found that the Delta variant replicates four times faster than the Alpha variant and nine times faster than the Beta variant.
• They also demonstrated that a recently discovered antiviral called thapsigargin successfully blocks the infection in cell cultures.

The success of the vaccination program in the fight against SARS-CoV-2, the virus that causes COVID-19, is being hampered by the virus continually mutating.

Many of the changes have little impact on the virus, but some alter how it spreads and the severity of the resulting disease. The mutations may also alter the performance of vaccines.

The World Health Organization (WHO) tracks all SARS-CoV-2 variants. The organization adds them to its list of variants of concern if they do any of the following:

• increase the speed at which the virus can spread
• increase the severity or change the symptoms of COVID-19
• decrease the available treatment options or the effectiveness of measures to control the virus

The current list includes the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) variants.

Mutations and coinfections

A recent study conducted at the University of Nottingham, in the United Kingdom, looked at the infection performance of theAlpha, Beta, and Delta variants in cell cultures.

The researchers studied the variants individually and together to understand what happens if a person contracts two variants at the same time — which is called coinfection.

The team also investigated the performance of thapsigargin, which the authors call a “recently discovered, broad-spectrum antiviral.”

The results appear in the journal Virulence.

The researchers found that the Delta variant replicated and spread between cells the quickest. It replicated four times faster than the Alpha variant and nine times faster than the Beta variant.

During coinfection, the Delta variant boosted the replication of both the Alpha and Beta variants. Replication was also quicker during coinfection with the Alpha and Delta or Alpha and Beta variants, compared with the sum of the individual replication rates.

Reports of breakthrough infections in fully vaccinated people highlight that vaccines cannot guarantee safety from a constantly changing target and that extra treatments are needed.

Antiviral treatment options

Antiviral drugs and similar medications can help the body fight off viruses, shorten the duration of viral infections, and reduce the symptoms of these illnesses.

According to the U.K.’s Medicines and Healthcare products Regulatory Agency, certain antivirals are safe and effective at reducing the risk of severe COVID-19 in at-risk people.

Antivirals work in different ways, depending the specific drug. The most common ways involve:

• blocking cell receptors so that viruses cannot bind to or enter healthy cells
• boosting the immune system and helping it fight off the virus
• reducing the amount of active virus in the body

Introducing thapsigargin

Thapsigargin is a biologically active compound found in the roots and fruits of the Mediterranean plant Thapsia Garganica, which is commonly known as deadly carrot.

Practitioners of folk medicine have used the compound for centuries to treat rheumatic pain, lung diseases, and infertility in females.

In an earlier study, the authors of the recent paperdemonstrated that in very small concentrations, thapsigargin blocks the replication of an early variant of SARS-CoV-2, as well as common cold and influenza viruses.

The most recent study, which was led by Kin-Chow Chang, a professor of veterinary molecular medicine at the university, investigated whether TG could block the newer SARS-CoV-2 variants.

The study showed that each variant was sensitive to the compound: A dose of thapsigargin before infection with the Alpha, Beta, or Delta blocked all of the infections in human cells. It also showed a 95% reduction in coinfection studies. Similarly, thapsigargin inhibited the replication of the variants in cells with preexisting infection.

“The antiviral state induced by a single priming dose of [thapsigargin] to cells lasts several days […] even without the ongoing presence of [the compound].” By contrast, “Conventional antivirals, such as molnupiravir and oseltamivir, require continuous minimum concentration levels in the body to inhibit the target virus.” Prof. Chang told Medical News Today.

He noted that “Producing an antiviral drug is technically much harder than producing a vaccine.” This is partly because current virus-centric antivirals, which target virus sites or stages of replication, can stop working over time as the virus mutates.

However, host-centric antivirals such as thapsigargin are “less susceptible to the development of virus resistance.”

The take-home message of this study is that thapsigargin may be a promising alternative way to combat COVID-19. The authors conclude:

“The antiviral potency of [thapsigargin] has now been extended to contemporary SARS-CoV-2 variants, including the [Delta] variant, in all combinations of single- and coinfections. We therefore submit that [thapsigargin] is potentially a truly broad-spectrum antiviral that targets a growing list of viruses.”

Prof. Chang says that “All research signs so far are encouraging and point to preclinical and clinical trials in the foreseeable future.” Although, he explains, it is “difficult to predict a time frame at this stage.”

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