A new paper has arrived genome biology and evolution, A paper published by Oxford University Press shows that the rapid evolution of the coronavirus disease 2019 (COVID-19) virus since 2019 has happened within a limited genetic pathway. These genetic limits have not changed. Despite scientists’ earlier concerns about the dramatic and rapid evolution of the COVID-19 virus, recent changes in the virus appear to have been relatively contained. Viruses changed by combining existing mutations. Viruses have not expanded the number of genetic pathways they follow to evolve.
SARS-CoV-2 has evolved rapidly since it first infected humans in late 2019, resulting in new virus variants with characteristics that make them successful in the human host. Previous studies have shown that these variants are not closely related to the major variants that were circulating earlier, leading many scientists to believe that changes in the structure of the spike protein (the spike or “crown” part in the familiar microscopic images of COVID-19) are driving the evolution of SARS-CoV-2 variants, allowing new mutations not previously possible in the virus.
The SARS-CoV-2 pandemic is the worst infectious disease pandemic in decades, causing worldwide deaths, economic damage, and social disruption. However, the response to the pandemic using modern technologies such as affordable mass sequencing has resulted in unique and important scientific datasets.
Researchers here took advantage of the scale of global genome sequencing, protein structure determination, and targeted research related to the virus. Using a rich dataset of SARS-CoV-2, they investigated the role of protein structural constraints in the evolution of SARS-CoV-2 and whether changes in the structure of the spike protein make the virus more potent. They applied multiple computational predictors of structural constraints across different structural backgrounds and assessed how constraints changed during the evolution of SARS-CoV-2 variants.
Research has found that SARS-CoV-2 has gone through several different evolutionary stages. The initial period of neutral diversification ended at the end of 2020 when multiple variants began to emerge. The World Health Organization has classified variants with suspected phenotypic characteristics, such as increased infectivity or immune evasion properties, as variants of concern. However, despite an unprecedentedly rich and detailed dataset, researchers have found no evidence that structural constraints change significantly or play a role in the evolution of SARS-CoV-2 S protein variants. Despite high mutation rates and strong selective pressure, the SARS-CoV-2 S protein was subject to strong structural constraints after being transferred to the human host.
Although SARS-CoV-2 evolved rapidly during the pandemic, the set of structurally viable mutations appears to have remained unchanged. This finding suggests that the emergence of variants results not from relaxation of structural constraints, but from new combinations of mutations and functional genetic interactions. However, overall evolution remained severely limited by the stability of the spike protein.
Our study investigates the dynamics of evolutionary changes in SARS-CoV-2 in the period after its spread to humans. We found that strong constraints acting on the viral spike protein limit possible mutations. This will help us understand how other coronaviruses behave as they move between species, and could have important implications for the design of future vaccines and antiviral drugs. ”
James Herzig, first author of the paper
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Oxford University Press USA
Reference magazines:
Thank you very much, HC, others. (2026) revealed that structural constraints acting on the SARS-CoV-2 spike protein limit the space for viral adaptation. Genome biology and evolution. DOI: 10.1093/live/evag049. https://academic.oup.com/gbe/article/doi/10.1093/gbe/evag049/8512735
