Objective: Nobody knows when the COVID-19 pandemic will end or when and where the next coronavirus will outbreak. Therefore, it is still necessary to develop SARS-CoV-2 inhibitors for different variants or even the new coronavirus. Since SARS-CoV-2 uses its surface spike-protein to recognize hACE2, mediating its entry into cells, ligands that can specifically recognize the spike-protein have the potential to prevent infection.

A universal aptamer against spike-proteins of diverse SARS-CoV-2 variants was discovered via DNA SELEX towards the wild-type (WT) spike-protein. This aptamer, A1C1, binds to the WT spike-protein or other variants of concern such as Delta and Omicron with low nanomolar affinities. A1C1 inhibited the interaction between hACE2 and various spike-proteins by 85–89%. This universal A1C1 aptamer can be used to design diagnostic and therapeutic molecular tools to target SARS-CoV-2 and its variants.

While monoclonal antibodies have shown success in cancer immunotherapy, their limitations prompt exploration of alternative approaches such as aptamers and peptides targeting programmed death ligand 1 (PD-L1). Despite the significance of these biotechnological tools, a comprehensive review encompassing both aptamers and peptides for PD-L1 targeting is lacking. Addressing this gap is crucial for consolidating recent advancements and insights in this field. Biotechnological advances leveraging aptamers and peptides represent a cutting-edge approach in refining the targeting proteins. Our review aims to provide valuable guidance for researchers and clinicians, highlighting the biotechnological advances utilizing aptamers and peptides refining PD-L1 targeting.