Convergent Evolution in SARS-CoV-2 Spike Creates a Variant Soup from Which New COVID-19 Waves Emerge

DANIELE FOCOSI; RODRIGO QUIROGA; SCOTT MCCONNELL; MARC C. JOHNSON; ARTURO CASADEVALL

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Lugar: Basel; Año: 2023 vol. 24

1422-0067

he first 2 years of the COVID-19 pandemic were mainly characterized by recurrent mutations of SARS-CoV-2 Spike protein at residues K417, L452, E484, N501 and P681 emerging independently across different variants of concern (Alpha, Beta, Gamma, and Delta). Such homoplasy is a marker of convergent evolution. Since Spring 2022 and the third year of the pandemic, with the advent of Omicron and its sublineages, convergent evolution has led to the observation of different lineages acquiring an additional group of mutations at different amino acid residues, namely R346, K444, N450, N460, F486, F490, Q493, and S494. Mutations at these residues have become increasingly prevalent during Summer and Autumn 2022, with combinations showing increased fitness. The most likely reason for this convergence is the selective pressure exerted by previous infection- or vaccine-elicited immunity. Such accelerated evolution has caused failure of all anti-Spike monoclonal antibodies, including bebtelovimab and