Search for RNA aptamers against non-structural protein of SARS-CoV-2: Design using molecular dynamics approach

Recent outbreak of deadly Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) urges the scientist to identify the potential vaccine or drug to control the disease. SARS-CoV-2 with its single stranded RNA genome (length ~ 30 kb) is enveloped with active spike proteins. The genome is non-segmental with 5'-cap and 3'-poly tail and acts as a mRNA for the synthesis of replicase polyproteins. The replicase gene lying downstream to 5'-end encodes for non-structural protein, which in turn pose multiple functions ranging from envelope to nucleocapsid development. This study aims to identify the highly stable, effective and less toxic single strand RNA-based aptamers against non-structural protein 10 (NSP10). NSP10 is the significant activator of methyltransferase enzymes (NSP14 and NSP16) in SARS-CoV-2. Inhibiting the activation of methyltransferase leads to partial viral RNA capping or lack of capping, which makes the virus particles susceptible to host defence system.

In this study, we focused on designing RNA aptamers through computational approach, docking of protein-aptamer followed by molecular dynamics simulation to perceive the binding stability of complex. Docking study reveals the high binding affinity of three aptamers namely RNA-053, 001, 010 to NSP10 with the HADDOCK score of - 88.5 ± 7.0, - 87.7 ± 11.5, - 86.1 ± 12 respectively. Molecular Dynamics suggests high conformational stability between the aptamer and the protein. Among the screened aptamers two aptamers maintained at least 3-4 intermolecular H-bonds throughout the simulation period.

The study identifies the potential aptamer candidate against less investigated but significant antiviral target i.e., NSP10/NSP16 interface complex.

The online version contains supplementary material available at 10.1186/s43088-021-00152-5.