Weekly inhaler puffs, similar to those used for asthma, might safeguard you against viral infections that could make winters challenging.

This promising idea stems from encouraging animal studies involving mRNA therapies aimed at activating our natural viral defenses. “We can consider this a universal antiviral agent,” states Dusan Bogunovic from Columbia University in New York.

To fully realize this potential, the development of mRNA technology used in vaccines will be essential, but recent funding cuts in the US for mRNA vaccine initiatives pose a significant concern. “I would be surprised if this doesn’t impact such progress,” Bogunovic mentioned.

Beyond recognizing and neutralizing viruses with antibodies, our bodies have multiple inherent defenses. For instance, upon detecting a viral invasion, cells emit a critical signaling molecule called interferons. This activates around 1000 genes, resulting in the production of various antiviral proteins, each playing distinct protective roles. Some obstruct viral entry into cells and hinder the release of other viral particles.

While not all antiviral proteins are effective against every virus, their strategic combination can yield significant results. “Our innate immune system is remarkably robust,” Bogunovic observes.

Bogunovic points out that the rapid replication of respiratory viruses presents a challenge. However, if the body can proactively prepare these defenses, it could reduce viral replication and ensure that infections remain less severe, even before the immune system fully kicks in.

There were hopes of using interferon as a broad-spectrum antiviral, but the potential for severe side effects warranted caution. Thus, Bogunovic and his team are focusing instead on creating an antiviral agent composed of a select group of 1000 proteins induced by interferons.

They chose 10 specific proteins and introduced them into cells via mRNAs that encode these proteins. The mRNA delivery system allows for temporary protein production within targeted cells, which is critical as preformed proteins are often too large to enter cells in adequate amounts.

Experiments where human cells were infected with a range of viruses, including influenza and Zika, demonstrated that this mRNA cocktail effectively enhanced viral protection. This could provide the necessary head start in the body.

The team subsequently administered these mRNAs to the lungs of Golden Hamsters. The mRNA combination afforded strong protection against the SARS-CoV-2 virus, which causes Covid-19, drastically reducing viral loads in comparison to untreated counterparts. “I thought, ‘This could actually be a universal antiviral,’” Bogunovic says.

Present antiviral medications are typically limited to specific viruses; hence, broad-spectrum treatments are immensely valuable. The breakthrough of antibiotics such as penicillin, which can eliminate a wide array of bacteria, has transformed medical practice.

Moreover, some combinations of proteins activated by interferons may work particularly well against specific viruses, Bogunovic mentions. This same methodology could also help in formulating specialized antiviral agents.

Effectively delivering mRNA to a significant number of vulnerable cells remains crucial. Further advancements are required, as targeting specific cell types with mRNA continues to be challenging.

“This scenario is certainly intriguing and could lead to significant developments, but we are still a distance from implementing practical and adaptable solutions,” states Aris Katzourakis from Oxford University. “This research emphasizes the vast potential of mRNA technology extending beyond vaccines. The current trend of mRNA vaccine funding in the US will likely and regrettably hinder progress in both domains.”

While antibiotic resistance remains a pressing issue, Bogunovic believes it is unlikely that viruses will develop resistance to this type of antiviral approach, given its combination of various interferon-triggered proteins that target multiple phases of the virus’s lifecycle. This combined strategy has already yielded successes in HIV treatments.