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Rapid assessment of SARS-CoV-2–evolved variants using virus-like particles

2021; American Association for the Advancement of Science; Volume: 374; Issue: 6575 Linguagem: Inglês

10.1126/science.abl6184

1095-9203

Abdullah M. Syed, Taha Y. Taha, Takako Tabata, Irene P. Chen, Alison Ciling, Mir M. Khalid, Bharath Sreekumar, Peiyi Chen, Jennifer M. Hayashi, Katarzyna M. Soczek, Mélanie Ott, Jennifer A. Doudna,

Animal Virus Infections Studies

Efforts to determine why new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants demonstrate improved fitness have been limited to analyzing mutations in the spike (S) protein with the use of S-pseudotyped particles. In this study, we show that SARS-CoV-2 virus-like particles (SC2-VLPs) can package and deliver exogenous transcripts, enabling analysis of mutations within all structural proteins and at multiple steps in the viral life cycle. In SC2-VLPs, four nucleocapsid (N) mutations found universally in more-transmissible variants independently increased messenger RNA delivery and expression ~10-fold, and in a reverse genetics model, the serine-202→arginine (S202R) and arginine-203→methionine (R203M) mutations each produced >50 times as much virus. SC2-VLPs provide a platform for rapid testing of viral variants outside of a biosafety level 3 setting and demonstrate N mutations and particle assembly to be mechanisms that could explain the increased spread of variants, including B.1.617.2 (Delta, which contains the R203M mutation).