COVID-19 Researchers Discover Hidden Pathway of Natural Immune Defense

An international cohort of scientists working on COVID-19 has discovered a hidden part of the human immune system that creates antiviral agents.

The discovery, published in the Journal of Proteome Researchwill enable the development of new tests for general active viral infection and new ways to create antiviral drugs that extend beyond COVID-19.

Led by Professor Julien Wist and Professor Jeremy Nicholson from the Australian National Phenome Center (ANPC) at Murdoch University in Perth, Western Australia, researchers from New Zealand, the United States, the United Kingdom and from Germany were analyzing blood and urine samples from COVID-19 patients. when they discovered a previously largely unknown element of the natural immune system that generates drug-like metabolites that act as antiviral agents.

Professor Nicholson, director of the ANPC, said they had detected 10 new compounds made by the body in response to the SARS Cov-2 virus.

The discovery of the extended VIPERIN pathway (X-VIP) has greatly expanded knowledge of the antiviral VIPERIN pathway, a part of the innate immune system that responds to most viral infections.

VIPERIN – short for interferon-inducible endoplasmic reticulum-associated virus inhibitory protein – is a multifunctional interferon-inducible protein that regulates virus replication. When a virus attacks the body, it triggers an interferon response and VIPERIN is believed to suppress virus replication.

“It is very unusual to discover significant new human biochemical pathways, especially those that could be of major medical importance,” Professor Nicholson said.

Professor Wist said that of the 10 X-VIP compounds detected, nine were new to human biology knowledge.

“These compounds are only produced during an active viral infection, and they have very short half-lives, so if we find them in a patient’s blood or urine, that patient is likely to be infectious and must self-isolate,” he said.

“X-VIP metabolites represent previously unknown biomarkers of infection and contagiousness and may be highly relevant for rapid diagnosis in severely infected hospitalized patients.

“It is fascinating that from a chemical perspective, these compounds ‘look like’ antiviral drugs and are very similar to some compounds already marketed by pharmaceutical companies as antiviral agents.

“This X-VIP opens the possibility of continuing studies aimed at designing new antiviral drugs.”

Of particular note, Professor Nicholson said, is that human biology contains the building blocks for the synthesis of antiviral drugs and that these have been helping to protect humans long before human medicine existed.

Professor Wist said the compounds were detected in both urine and plasma, and a simple non-invasive urine test could also be developed for rapid detection.

“In fact, we have already demonstrated proof of principle that we could deploy a rapid urine test to diagnose active viral infections that could be of considerable medical importance,” he said.

Dr Samuele Sala, leader of the study, said the genetic evidence suggested the processes were ancient.

“It seems that nature created a mechanism to fight viruses billions of years before humans even existed,” he said.

“Genomic evidence from other research indicates that the VIPERIN gene was present in very ancient organisms, possibly including ancestors of stromatolites, whose descendants happen to live off the coast of Western Australia.”

Professor Nicholson said COVID-19 had received unprecedented clinical and scientific scrutiny since its global emergence in late 2019.

COVID-19 manifests as a respiratory illness, but also affects all major organs. For some people, these impacts, combined with prolonged disruptions to the immune system, can lead to long-term or post-acute COVID-19 syndrome (PACS).

ANPC has advanced global research in understanding the infection pathways and biological consequences of COVID-19, including long COVID. The Center deploys broad and in-depth metabolic analysis of blood plasma and urine samples using NMR (nuclear magnetic resonance), mass spectrometry and cutting-edge data modeling.

“ANPC examines the complex interactions between disease genetics, environment and lifestyle,” Professor Nicholson said.

“Understanding why symptom severity in COVID-19 patients is so variable and discovering early markers that accurately define the likely impact on an individual patient is critical to mitigating current patient health impacts and responding effectively to other pandemic viruses that may emerge in the future. »