Design and application of SARS-CoV-2 Delta variant virus-like particles (VLPs) in aptamer-based diagnostic assay development

The emergence and rapid evolution of SARS-CoV-2 variants present various implications towards public health and research. Viral propagation necessitates biosafety level 3 (BSL-3) containment, while the mutations harboured by the variants pose diagnostic challenges. These led to the exploration of virus-like particles (VLPs), which closely mimic the morphology of the virus but are non-infectious and safer to handle. While the diagnostics and therapeutics of COVID-19 predominantly rely on antibodies, aptamers are increasingly recognised as an alternative molecular recognition element. Aptamers are single-stranded nucleic acids that bind target molecules with high specificity and affinity. Their advantages over antibodies include lower production costs, faster synthesis, ease of chemical modification, and minimal batch-to-batch variability. Existing anti-SARS-CoV-2 aptamers can be further improved through rational design approaches, such as truncation, base substitution, 3’-polyadenylation, and multimerisation. In this study, aptamers were refined and employed in the development of an enzyme-linked aptasorbent assay (ELASA) for SARS-CoV-2 Delta variant VLPs detection, which were first generated as safe and functional surrogates for the native virus.