A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused a large respiratory outbreak in Wuhan, China in December 2019, is currently spreading across many countries globally. Here, we show that a TMPRSS2expressing VeroE6 cell line is highly susceptible to SARS-CoV-2 infection, making it useful for isolating and propagating SARS-CoV-2. Our results reveal that, in common with SARS-and Middle East respiratory syndrome-CoV, SARS-CoV-2 infection is enhanced by TMPRSS2.

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We previously reported that the Japanese encephalitis virus (JEV) strain Mie/41/2002 has weak pathogenicity compared with the laboratory strain Beijing-1. To identify the determinants of its growth nature and pathogenicity, we produced intertypic viruses, rJEV(EB1-M41), rJEV(nEB1-M41) and rJEV(cEB1-M41), which contained the entire, the N-terminal, and the C-terminal half, respectively, of the Beijing-1 E region in the Mie/41/2002 background. The growth of rJEV(EB1-M41) in mouse neuroblastoma N18 cells and virulence in mice were similar to those of Beijing-1. rJEV(nEB1-M41) propagated in N18 cells to the same extent as did Beijing-1. Furthermore, we produced mutant viruses with single amino acid substitutions in the N-terminal half of the Mie/41/2002 E region. A Ser-123-Arg mutation in the Mie/41/2002 E protein exhibited significantly increased growth rate in N18 cells and virulence in mice. These results indicate that the position 123 in the E protein is responsible for determining the growth properties and pathogenicity of JEV.

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In this study, the anti–severe acute respiratory syndrome coronavirus‐2 (anti‐SARS‐CoV‐2) activity of mycophenolic acid (MPA) and IMD‐0354 was analyzed. These compounds were chosen based on their antiviral activities against other coronaviruses. Because they also inhibit dengue virus (DENV) infection, other anti‐DENV compounds/drugs were also assessed. On SARS‐CoV‐2‐infected VeroE6/TMPRSS2 monolayers, both MPA and IMD‐0354, but not other anti‐DENV compounds/drugs, showed significant anti‐SARS‐CoV‐2 activity. Although MPA reduced the viral RNA level by only approximately 100‐fold, its half maximal effective concentration was as low as 0.87 µ m, which is easily achievable at therapeutic doses of mycophenolate mofetil. MPA targets the coronaviral papain‐like protease and an in‐depth study on its mechanism of action would be useful in the development of novel anti‐SARS‐CoV‐2 drugs.