SARS-CoV-2 Membrane Protein Inhibits NLRP3 Inflammatory Body And Weakens Inflammatory Response

Aim: We screened the protein components encoded by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),analyzing the relationship between the membrane protein(M protein)and the inflammatory factor Interleukin-1 beta(IL-1β).We explored the molecular mechanism of SARS-CoV-2 M protein inhibiting NLRP3 inflammasome activation and attenuating inflammatory response,which is expected to provides new research ideas and new therapeutic targets for the treatment of SARS-CoV-2.Methods: Firstly,cells were transfected with plasmids encoding various structural proteins(E,N,M)and accessory proteins(3a,6,7a,8,10)genes of SARS-CoV-2.We used Western blot and enzyme-linked immunosorbent assay(ELISA)to screen viral proteins that can inhibit the inflammatory factor IL-1β.The relationship between the SARS-CoV-2 protein and the NLRP3 inflammasome in the inflammatory pathway was further explored by real-time quantitative PCR(q PCR)and ELISA.Next,the association between the M protein of SARS-CoV-2 and the NLRP3 protein in the NLRP3 inflammasome was explored by using co-immunoprecipitation(CO-IP)and immunofluorescence experiments.Then,we further explored whether the interaction between SARS-CoV-2 M protein and NLRP3 protein affects the oligomerization of ASC and directly affects the assembly of NLRP3 inflammasome by ASC oligomerization experiments.Results: Inhibition of the NLRP3 inflammasome by the SARS-CoV-2 M protein results in a decrease in the inflammatory factor IL-1β.The molecular mechanism leading to this phenomenon is that M protein interacts with NLRP3 protein,inhibiting the interaction between NLRP3 protein and ASC protein,thereby inhibiting the assembly and activation of NLRP3 inflammasome and reducing inflammatory cytokines IL-1β production to attenuate the inflammatory response.Conclusion: SARS-CoV-2 M protein plays a key role in inhibiting the body’s NLRP3-related inflammatory response,providing a strategy for the treatment of SARS-CoV-2.