The SARS-CoV-2 SSHHPS Recognized by the Papain-like Protease

Area of Science:

• Virology
• Molecular Biology
• Proteomics

Background:

• Viral proteases recognize specific cleavage sites, often involving host-pathogen sequence homology.
• Over 40 host proteins are known targets for certain viral proteases, indicating significant host-pathogen interactions.

Purpose of the Study:

• To identify specific human host proteins cleaved by viral proteases, particularly SARS-CoV-2 papain-like protease (PLpro).
• To explore the potential for extracting viral pathogenesis information from viral genome sequences.

Main Methods:

• Utilized PHI-BLAST to search the human proteome for sequences homologous to viral protease cleavage sites.
• Analyzed identified host protein targets for their relevance to viral infection and pathogenesis.
• Performed in vitro cleavage assays for SARS-CoV-2 PLpro.

Main Results:

• Identified MYH7, MYH6 (cardiac myosins), FOXP3 (Treg transcription factor), ErbB4, and PROS1 (anticoagulation protein) as novel in vitro targets of SARS-CoV-2 PLpro.
• Observed that zinc inhibited the in vitro cleavage of these host sequences.
• Noted patterns in multispecies sequence alignments suggesting implications for animal models and zoonosis.

Conclusions:

• Viral proteases cleave diverse host proteins beyond immune response modulators, including those linked to cardiomyopathies and anticoagulation.
• The identified cleavage sites provide potential insights into viral pathogenesis and host-pathogen interactions.
• Further research into these interactions may inform animal model selection and understanding of zoonotic potential.