As a virus infects and makes copies of itself in the body, the genetic code can change. These changes are called mutations. Some mutations make the virus better at infecting cells, spreading and causing illness. Others may help the virus avoid the immune system or cause tests for the virus to be less accurate.
After SARS-CoV-2 circulating for more than a year in the human population, highly mutated variants emerged, called variants of concern (VOCs). They differed from one another in their intrinsic functional properties such as transmissibility and antigenicity, which enable them to escape from primed host immune responses. Each VOC emerged independently and rapidly became dominant in a regional or global context, outcompeting previous variants.
The most common signature mutation in COVID-19 variants is D614G, an aspartic acid-to-glycine substitution in the spike protein. This mutation increases the viral attachment to ACE2 receptors on host cells and facilitates entry into infected cells. It is usually accompanied by two other mutations in RNA-dependent RNA polymerase (RdRp): a silent C-to-T mutation in the 5’ untranslated region and a C-to-T at position 14408 of RdRp that alters amino acids in the substrate binding domain. Remdesivir targets these RdRp mutations and inhibits their activity.
Several studies suggest that the D614G mutation increases viral replication in respiratory epithelial cells. It also enhances viral titers in the nose and throat of infected people, suggesting that it may make them more infectious to other people. The D614G mutation also seems to affect the ability of antibodies to neutralize the virus. The most widespread variant in late 2024, Omicron, is known to evade vaccine- and infection-acquired immunity and resists treatment with ribavirin.