SARS-CoV-2 encodes a viral deISGylase called PLpro, but its physiological functions and direct substrates remain elusive. Using a deISGylation-activity-ablated recombinant SARS-CoV-2, Zhu et al. show that deISGylation activity is required for innate immune evasion and, furthermore, relieves metabolic restriction of viral replication by modulating the activity of key enzymes in glycolysis, the pentose phosphate pathway, and redox homeostasis.

Read the full paper: Host OTUB2 and viral PLpro stabilize NSP8 to promote SARS-CoV-2 replication

Read the full paper: Genetically Encoded Fluorescent Sensors for SARS-CoV-2 Papain-like Protease PLpro

The COVID-19 pandemic caused by SARS-CoV-2 has resulted in millions of deaths worldwide. Despite the emergence of antiviral drugs and vaccines targeting 3CLpro and RNA-dependent RNA polymerase (Rdrp), the virus’s continuous mutation underscores the need for novel therapeutic approaches that target highly conserved viral regions. PLpro is an attractive target due to its roles in viral replication and host immune regulation. However, research on nanobodies targeting PLpro remains in its infancy. This study provides significant insights into the antiviral and anti-inflammatory functions of two nanobodies, NbP1 and NbP2, which specifically disrupt the PLpro/ISG15 interaction interface. Our findings have important implications for drug development targeting SARS-CoV-2, highlighting the potential of nanobody-based therapeutics to simultaneously inhibit viral replication and suppress pathological inflammation.

Coronaviruses are a large family of viruses capable of causing severe respiratory diseases, with recent outbreaks posing major threats to global public health. The SARS-CoV-2 papain-like protease (PLp...

A novel antiviral targeting the SARS-CoV-2 PLpro protease shows strong efficacy in a mouse model, preventing lung pathology and reducing brain dysfunction. The study provides proof-of-principle that P...

A novel antiviral targeting the SARS-CoV-2 PLpro protease shows strong efficacy in a mouse model, preventing lung pathology and reducing brain dysfunction. The study provides proof-of-principle that P...

Viral proteases play critical roles in the host cell and immune remodeling that allows virus production. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) papain-like protease (PLpro...

Viral proteases play critical roles in the host cell and immune remodeling that allows virus production. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) papain-like protease (PLpro...

Orally active SARS-CoV-2 papain-like protease inhibitors demonstrate in vivo efficacy in a murine infection model.

Jia-Li Lu, Yue Yin, Xiao-Long Zhou; A non-proteolytic role of SARS-CoV-2 PLpro in modulating host glycyl-tRNA synthetase activity, Journal of Molecular Cel

Papain-like protease from SARS-CoV-2 plays an important role in the cleavage of the viral polyproteins and in the suppression of the host's immune response. Here, we present the results of an NMR scr...

A novel antiviral targeting the SARS-CoV-2 PLpro protease shows strong efficacy in a mouse model, preventing lung pathology and reducing brain dysfunction. The study provides proof-of-principle that P...

SARS-CoV-2 encodes a viral deISGylase called PLpro, but its physiological functions and direct substrates remain elusive. Using a deISGylation-activity-ablated recombinant SARS-CoV-2, Zhu et al. show that deISGylation activity is required for innate immune evasion and, furthermore, relieves metabolic restriction of viral replication by modulating the activity of key enzymes in glycolysis, the pentose phosphate pathway, and redox homeostasis.

The global battle against SARS-CoV-2, the virus behind COVID-19, continues to evolve. While the pandemic may be winding down, the virus and its capacity to mutate remain a significant challenge to pub...