Recently, a team of scientists from the Indian Institute of Science, Bangalore, published a promising finding in Cell Reports Medicine. They investigated how Picolinic acid (PA), a natural compound, could be used to treat pandemic viruses like SARS-CoV‑2 and Influenza A.

Viruses that cause diseases, also known as pathogenic viruses, undergo continuous evolution, posing significant challenges to treat them effectively. The problem becomes more complicated when viruses develop resistance, making treatment even harder. In a study published in 2018, scientists showed that PA has antiviral properties, which led them to explore how it could affect the prevalent Influenza virus. When the COVID-19 pandemic started, they also looked into its effects on the SARS-CoV‑2 virus.

Viruses, whether enveloped or non-enveloped, use two primary methods to infect cells: they either merge directly with the cell membrane or get inside through a process known as endocytosis. This is when the virus is taken into the cell and encapsulated within a structure called an endosome. Once inside, the virus multiplies and spreads, causing an infection. So, focusing on stopping the virus from entering the cell holds great promise as a strategy for developing treatments against viral infections.

Shashank Tripathi, Assistant Professor, IISc, Bangalore, and corresponding author of the study, highlighted, 

Previous research showed that PA can slow down the endocytosis process. This observation led to the hypothesis that PA might have a broad-spectrum activity, since many viruses use the endocytic pathway as a common way to enter cells.

To substantiate this hypothesis, the researchers performed several cell-based assays on various viruses. Tripathi further added, ​“The results clearly showed that PA has a broad-spectrum antiviral activity, especially against enveloped pathogenic viruses such as SARS-CoV‑2 and Influenza A,”. This study underlines the PA’s potential as a treatment that can focus on and hinder the way viruses enter cells, opening new avenues for effectively fighting viral infections.

Researchers conducted in-vitro studies on various cell lines to gain a deeper insight into how PA works. These studies were crucial in pinpointing the specific stage of virus entry that PA targets. The findings revealed that PA disrupts the protective layer around the virus called viral envelope, stopping it from entering the cell and merging with the cell membrane. However, it was observed that PA had little to no effect on non-enveloped viruses. These observations further supported the findings that PA operates through a distinct and selective mechanism, primarily aimed at the viral envelope. This approach addresses the issue at its core by effectively targeting factors within the host cell, which reduces the risk of viruses becoming resistant through mutations.

To thoroughly assess how effective PA is against viral infections, researchers conducted experiments in living organisms called in-vivo studies using animal models. Giving them PA had noteworthy outcomes, including a significant reduction in viral load, noticeable improvement in symptoms, and increased survival rates. What’s particularly interesting is that PA showed effects on the immune system, making it more responsive and stronger. This likely contributed in its ability to fight viruses. These findings highlight the potential of PA as a treatment for viral infections and suggest that it can enhance the immune system’s ability to defend against viruses.

Tripathi asserted that this study has shown how PA irreversibly impacts the viral envelope, making it a strong inhibitor against a wide range of viruses, i.e. a highly potent broad-spectrum inhibitor. Nonetheless, he emphasised the need for further research to comprehend how the body processes and releases the metabolite. He underscored the importance of rigorous clinical studies to confirm its effectiveness as a treatment for humans.

Indranil Banerjee, Assistant Professor, Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, commended this elegant strategy that targets the virus in its early life cycle stage. He expressed his belief that the study holds significant promise for therapeutic applications. However, Banerjee also stressed the importance of additional research to fully grasp how PA works within the viral envelope.