With over 700 million infections and nearly seven million deaths, the SARS-CoV-2 virus has caused the most devastating pandemic of the 21st century. While vaccines and medication have helped mitigate the impact of COVID-19, the constant mutation of the virus poses an ongoing threat. In a molecular arms race against the human immune system, the virus has developed various strategies to evade its defenses.
In a breakthrough discovery, a team of researchers from the University of Göttingen has identified protective switches within the coronavirus that shield it from attacks by the immune system. The findings, published in Nature Communications, highlight two previously unknown chemical protective switches in the virus’s main protease—a crucial protein for the coronavirus.
The leading drug against COVID-19, Paxlovid, targets this protein, which the virus uses to replicate itself by cutting out other virus proteins in infected cells. The researchers found that the coronavirus utilizes the amino acid cysteine for this process, and cysteines can be destroyed by highly reactive oxygen radicals produced by the immune system to fight viruses.
However, the protective switches in the virus’s main protease defend it against the immune system’s oxygen radical bombardment. One cysteine forms a disulfide bond with an adjacent cysteine, preventing its destruction. Additionally, a bridge known as SONOS connects three parts of the protein, effectively safeguarding its three-dimensional structure from damage by radicals.
Professor Kai Tittmann, from Göttingen University’s Molecular Enzymology Research Group, explains that this discovery showcases the coronavirus’s remarkable ability to defend itself against the immune system. Interestingly, the protective switches were also found in the earlier coronavirus SARS-CoV-1, responsible for the 2002-2004 outbreak. This is the first time such switches have been identified.
However, the researchers did not stop at the discovery. Armed with the chemical blueprint, they conducted a search for molecules that can bind precisely to these protective switches and inhibit the virus’s main protease. Their search yielded promising results, with the identification of molecules that could bind to the switches in both test tubes and infected cells.
Lisa-Marie Funk, the first author of the study and a member of Göttingen University’s Molecular Enzymology Research Group, highlights the potential for new therapeutic interventions derived from these findings. Targeting the protective switches could offer a way to halt the replication of coronaviruses and combat future outbreaks effectively.
This breakthrough discovery paves the way for further research into the development of drugs and treatments that can effectively target the protective switches in SARS-CoV-2 and other coronaviruses. By understanding the mechanisms by which the virus evades immune responses, scientists can work towards more effective strategies in the ongoing battle against COVID-19 and future pandemics.
1. Source: Coherent Market Insights, Public sources, Desk research
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