Picolinic: Picolinic acid, a natural compound in humans, can block viruses like SARS-CoV2: IISc

BENGALURU: A new study by researchers at the Indian Institute of Science (IISc) and their collaborators has found that Picolinic acid, a natural compound produced by mammalian cells, can block several disease-causing viruses such as SARS-CoV-2 — the virus causing Covid-19 — and influenza A viruses. The study has been published in the journal Cell Reports Medicine.
“The study describes the compound’s remarkable ability to disrupt the entry of enveloped viruses into the host’s cell and prevent infection. Researchers hope to develop the compound into a broad-spectrum therapeutic that can help fight against a variety of viral diseases,” IISc said in a statement.
While Picolinic acid is known to help in the absorption of zinc and other trace elements from our gut, in its natural form, it stays inside the body only for a short duration as it’s usually excreted out. In recent years, IISc said, scientists have begun noticing that it may also exhibit antiviral activity.
“A few years ago, the IISc team began investigating endocytosis, a cellular process often co-opted by viruses and bacteria to enter our cells. During their investigations, researchers stumbled upon picolinic acid and realised it could slow down viral entry into host cells,” IISc said, adding that they then decided to test Picolinic acid’s antiviral potential.
Shashank Tripathi, assistant professor at IISc’s Department of Microbiology and Cell Biology (MCB) and the Centre for Infectious Diseases Research (CIDR), said that coincidentally, the pandemic emerged during the study. “So, we extended our research to examine its impact on SARS-CoV-2 and found it to be even more potent in this context,” Tripathi, also a corresponding author of the study, said.
Picolinic acid displayed a preference for blocking enveloped viruses. “In addition to the usual protein coat found in all viruses, these enveloped viruses have an extra outer membrane made of lipids derived from the host. This envelope is crucial for virus entry into its target cell. Incidentally, a majority of human viruses with high prevalence and pandemic potential are enveloped viruses,” IISc said.
It added that during their entry into host cells, viruses envelope and host cell membrane fuse, creating a pore through which viruses’ genetic material enters and starts replicating. Researchers found that picolinic acid specifically blocks this fusion, which explains its effectiveness against a variety of enveloped viruses, including flaviviruses like the Zika virus and the Japanese encephalitis virus.
The compound did not have much effect on non-enveloped viruses like rotavirus and coxsackievirus, IISc said, adding that usually, antiviral drugs target either the virus directly – which can sometimes lead to drug resistance – or some part of the host cell, which may lead to negative side-effects.
“This compound, on the contrary, stands out because it falls in between… it’s targeting a host-derived component of the virus. Since viruses borrow this component from the host, they don’t have the machinery to repair the damage to their envelope. So, with the same compound, you are damaging the virus permanently, while causing a very transient minimal effect on the host cell with self-repair ability,” Tripathi explained.
When the compound was tested in SARS-CoV-2 and influenza animal models, it protected animals from infection. It also reduced viral load in the lungs when given to infected animals, while researchers also found picolinic acid led to an increase in immune cells in the animals.
Rohan Narayan, research associate, CIDR and first author of the paper, said: “Our focus is on enhancing the compound’s efficacy, stability and absorption in the host body. We’re seeking partnerships with pharmaceutical industries to facilitate its clinical development and use against present as well as impending viral outbreaks.”