MERS-CoV and SARS-CoV-2 replication can be inhibited by targeting the interaction between the viral spike protein and the nucleocapsid protein

• Published in: Theranostics Vol. 11; no. 8; pp. 3853 - 3867
• Main Authors: Park, Byoung Kwon, Kim, Jinsoo, Park, Sangkyu, Kim, Dongbum, Kim, Minyoung, Baek, Kyeongbin, Bae, Joon-Yong, Park, Man-Seong, Kim, Won-Keun, Lee, Younghee, Kwon, Hyung-Joo
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 01.01.2021; Ivyspring International Publisher
• Subjects: Animals; Cell culture; Cell cycle; Chlorocebus aethiops; Cloning; Coronavirus Nucleocapsid Proteins - metabolism; Coronaviruses; COVID-19; Disease transmission; Fatalities; Genomes; Infections; Middle East respiratory syndrome; Middle East Respiratory Syndrome Coronavirus - physiology; Penicillin; Peptides; Phosphoproteins - metabolism; Phylogeography; Polyclonal antibodies; Protein Binding; Protein Interaction Domains and Motifs; Proteins; Research Paper; Respiratory diseases; SARS-CoV-2 - physiology; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - metabolism; Vero Cells; Virus Replication; Viruses; United States > US; South Korea; nucleocapsid protein; SARS-CoV-2; targeting; MERS-CoV; spike protein
• ISSN: 1838-7640; 1838-7640
• DOI: 10.7150/thno.55647

The molecular interactions between viral proteins form the basis of virus production and can be used to develop strategies against virus infection. The interactions of the envelope proteins and the viral RNA-binding nucleocapsid (N) protein are essential for the assembly of coronaviruses including the Middle East respiratory syndrome coronavirus (MERS-CoV). Using co-immunoprecipitation, immunostaining, and proteomics analysis, we identified a protein interacting with the spike (S) protein in the cells infected with MERS-CoV or SARS-CoV-2. To confirm the interaction, synthetic peptides corresponding to the C-terminal domain of the S protein (Spike CD) were produced and their effect on the interaction was investigated . effect of the Spike CD peptides after cell penetration was further investigated using viral plaque formation assay. Phylogeographic analyses were conducted to deduce homology of Spike CDs and N proteins. We identified a direct interaction between the S protein and the N protein of MERS-CoV that takes place during virus assembly in infected cells. Spike CD peptides of MERS-CoV inhibited the interaction between the S and N proteins Furthermore, cell penetration by the synthetic Spike CD peptides inhibited viral plaque formation in MERS-CoV-infected cells. Phylogeographic analyses of Spike CDs and N proteins showed high homology among betacoronavirus lineage C strains. To determine if Spike CD peptides can inhibit the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we used the same strategy and found that the SARS-CoV-2 Spike CD peptide inhibited virus replication in SARS-CoV-2-infected cells. We suggest that the interaction between the S protein and the N protein can be targeted to design new therapeutics against emerging coronaviruses, including SARS-CoV-2.