Role of Dengue in SARS-CoV-2 Evolution in Dengue Endemic Regions

Evidence suggests that dengue virus (DV) antibodies (Abs) and SARS-CoV-2 Abs were cross-reactive, resulting in reciprocal serological cross-interaction and providing cross-protection in populations in co-endemic regions. It became apparent from the present study that SARS-CoV-2 variants were preferentially selecting mutation(s)/deletions in the spike to evade interaction with DV Abs. We looked at mutations in the SARS-CoV-2 spike protein and how they affected the antigenicity, focusing on successively emergent major variants such as B.1.1.7 (Kent), B.1.617 (Delta), B.1.617.2.1 (Delta-Plus), B.1.1.529 (Omicron-BA.1) and B.1.1.529 (Omicron-BA.2). To further understand the effect of cross-reactive DV Abs on SARS-CoV-2 spike mutation(s), structural studies and docking simulations were performed using DV-2 envelope (E) Abs. Signature mutation (s) in spike variants implied that majority of the above changes in the spike were driven by DV Abs rather than immune pressure of SARS-CoV-2 (preceding variants). This was supported by the fact that the lately emergent SARS-CoV-2 variants like Omicrons (2022-23) were at least 50% less cross-reactive to DV compared to preceding predominant strains. This was further supported by the observed cross-binding of pre-pandemic DV Ab-positive serums to spike synthetic peptides in ELISA, designed from certain regions of the spike RBD which showed maximum cross-interactions with DV E Abs.