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

Background: 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 similar to 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. Results: 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. Conclusions: The study identifies the potential aptamer candidate against less investigated but significant antiviral target i.e., NSP10/NSP16 interface complex.

Automated summary

This study aims to identify stable and effective single strand RNA-based aptamers against NSP10 in SARS-CoV-2. Through computational approach, protein-aptamer docking and molecular dynamics simulation, the study revealed high binding affinity and conformational stability between the aptamers and the protein.