Exploring the mutation landscape of SARS-CoV-2 Variant JN.1

Abstract

Although Covid-19 is no longer a global pandemic, the spread of SARS-CoV-2 variants, currently led by Omicron and its subvariant, remains prevalent worldwide and causes health issues. In mid-2023, a descendant of BA.2, BA.2.86, carries more than 30 mutations in the Receptor Binding Domain (RBD), helping this variant transmit to create thousands of new COVID-19 cases in many countries worldwide. JN.1 was determined as a descendant of BA.2.86 by WHO because of the mutation profile in spike protein. JN.1 transmission is currently in Europe, the United States and other countries. Therefore, examining unique mutations in RBD of JN.1 to bind with hACE2 plays an important role in discovering the infectious efficiency of this variant. Our study shows that JN.1 has a lower affinity for hACE2 than the ancestral variant BA.2.86. In particular, L455S mutation reduces binding free energy by decreasing Van der Waals interaction energy. We also provide new insights into the significance of E484K in the RBD of JN.1, helping to bind stable with hACE2. Collectively, we suggest that residues positively charged in the RBD of JN.1 play the most important role in the interaction mechanism with hACE2. Future new variants should emphasize positively charged amino acid substitutions in the RBD.