Papain-like protease, an important target of anti-SARS-CoV-2 viral drugs

Recently, the journal "Nature" reported the latest research results on the treatment of new coronary pneumonia. Researchers from Germany and the Netherlands found that inhibiting papain-like protease is expected to become a new strategy for the treatment of COVID-19.

Previous studies have shown that protease has an important function in the replication cycle of coronavirus and is an important target protein for anti-coronavirus drug research.

The papain-like protease PLpro is an essential coronavirus enzyme required for processing viral polyproteins to generate a functional replicase complex and enable viral spread. PLpro is also implicated in cleaving proteinaceous post-translational modifications on host proteins as an evasion mechanism against host anti-viral immune responses. The papain-like protease contained in the SARS-CoV-2 virus protein has two functions: it not only plays a role in the maturation and release of new virus particles, but also inhibits the production of type 1 interferon.

The production of type 1 interferon in immune cells is caused by the recognition of the special components of the pathogen by the host cell's pattern recognition receptors. When the new coronavirus invades the human body, the cells will release type 1 interferon messenger molecules, and they will recruit Natural killer cells are used to kill infected cells, so type 1 interferon is considered to be the main contributor to the antiviral response. The behavior of papain-like protease to inhibit the production of type 1 interferon will break the body's defense mechanism, thereby helping the new coronavirus to invade the body quickly.

The inhibition of SCoV2-PLpro with GRL-0617 impairs the virus-induced cytopathogenic effect, fosters the anti-viral interferon pathway and reduces viral replication in infected cells. These results highlight a dual therapeutic strategy in which targeting of SCoV2-PLpro can suppress SARS-CoV-2 infection and promote anti-viral immunity.

Reference: Donghyuk Shin et al. Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity. Nature, 2020, doi:10.1038/s41586-020-2601-5.