Figure 1.

Replication-Associated Generation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants.

Replication-associated mutations and intrinsic selection factors play a critical role in the evolution and subsequent emergence of SARS-CoV-2 variants from infected cells. SARS-CoV-2 genome [positive (+) sense single stranded (ss)RNA] is released into the cytoplasm after virus binding to the angiotensin-converting enzyme 2 (ACE2) receptor and entry (A; red strand). The viral replicase complex transcribes the genome into negative (–) sense ssRNA (B; green strand) which acts as a template for subsequent synthesis of full-length +sense ssRNA genome copies (C). During replication, errors introduce mutations within the SARS-CoV-2 genome (D), which lead to mutations within viral proteins (E). While one copy of the genome is packaged into each SARS-CoV-2 virion (F), the heterogeneity of spike proteins on the surface of each virion (represented by different colors) remains unknown. Finally, SARS-CoV-2 variants carrying +sense ssRNA genomes with a varying number of mutations are released from the infected cell following egress (G).