Apart from its structural role that confers metal chelating properties, picolinic acid has been known to play vital roles against neurotoxicity, osteoporosis, and depression. Over the years, picolinic acid has shown to exhibit antiviral activity. The recent pandemic has placed the kynurenine pathway in the spotlight, as we previously covered details in our Newsletter issue 1, and more recently, it has been implicated in long COVID, as described in our featured article (see 2022 August issue). Now, we have further evidence that picolinic acid may play an important role against COVID.
Narayan et al showed that picolinic acid is a broad-spectrum antiviral agent that specifically targets enveloped viruses, including SARS-CoV-2 and influenza A viruses. Picolinic acid exerts its effect by blocking cellular membrane fusion, thereby inhibiting viral entry into the host cell. In contrast, picolinic acid is ineffective against non-enveloped viruses. Preclinical data showed promising therapeutic effects of exogenous administration of picolinic acid at a non-toxic dosage to attenuate SARS-CoV-2 infection in an animal model.
Piecing this together, neuropathy and depression have been observed in (long) COVID, which is associated with increases in the Kyn/Trp ratio and quinolinic acid levels. Considering the enzyme ACMSD that governs the switch between quinolinic and picolinic acids production, it is not hard to envisage that a therapeutic strategy to increase picolinic acid production would have multiple beneficial effects in neuroprotection, promoting bone health, and acting as an anti-depressant. As is demonstrated here picolinic acid therapy may also act as an antiviral for certain viruses and would be especially beneficial in the geriatric population, being the most vulnerable group of COVID.