A serum-stable RNA aptamer specific for SARS-CoV-2 neutralizes viral entry

Valero, Julián; Civit, Laia; Dupont, Daniel M.; Selnihhin, Denis; Reinert, Line S.; Idorn, Manja; Israels, Brett; Bednarz, Aleksandra; Bus, Claus; Asbach, Benedikt; Peterhoff, David; Pedersen, Finn Skou; Birkedal, Victoria; Wagner, Ralf; Paludan, Søren R.; Kjems, Jørgen

doi:10.1073/pnas.2112942118

Cited by 79 publications

(111 citation statements)

References 61 publications

Supporting

Mentioning

109

Contrasting

Order By: Relevance

“… 10 A trimeric RNA aptamer was shown to neutralize wild-type SARS-CoV-2 entry to cells. 28 Therefore, designed SCORe.50 dimers that connect two SCORe.50 with a 12-, 20-, or 30-nt stretch of A–T complementary binding to augment binding affinity for Omicron RBD ( Figure S7A ). We first show costaining between fluorescently labeled SCORe.50 and BA.1 RBD binding to ACE2-overexpressing cells ( Figure S7B ).…”

Section: Resultsmentioning

confidence: 99%

SCORe: SARS-CoV-2 Omicron Variant RBD-Binding DNA Aptamer for Multiplexed Rapid Detection and Pseudovirus Neutralization

et al. 2022

View full text Add to dashboard Cite

During the COVID-19 (coronavirus disease 2019) pandemic, several SARS-CoV-2 variants of concern emerged, including the Omicron variant, which has enhanced infectivity and immune invasion. Many antibodies and aptamers that bind the spike (S) of previous strains of SARS-CoV-2 either do not bind or bind with low affinity to Omicron S. In this study, we report a high-affinity S ARS- C oV-2 O micron R BD-binding aptam e r (SCORe) that binds Omicron BA.1 and BA.2 RBD with nanomolar K D1 . We employ aptamers SCORe.50 and SNAP4.74 in a multiplexed lateral flow assay (LFA) to distinguish between Omicron and wild-type S at concentrations as low as 100 pM. Finally, we show that SCORe.50 and its dimerized form SCOReD can neutralize Omicron S-pseudotyped virus infection of ACE2-overexpressing cells by >70%. SCORe therefore has potential applications in COVID-19 rapid diagnostics as well as in viral neutralization.

show abstract

Section: Resultsmentioning

confidence: 99%

SCORe: SARS-CoV-2 Omicron Variant RBD-Binding DNA Aptamer for Multiplexed Rapid Detection and Pseudovirus Neutralization

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The screening procedures of structure similarity, docking, and MD simulations can be applied to perform the in-silico selection of aptamers for screening a large number of mutated sequences. The computational results obtained from our study reveal that the RBD-1CM1 aptamer can have strong interactions with the RBD of the S1 subunit, which also has the potential for diagnosis applications, such as in rapid test kits [ 12 ] and aptamer-based biosensors [ 11 ], or for the treatment of SARS-CoV-2 [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

In-Silico Selection of Aptamer Targeting SARS-CoV-2 Spike Protein

Lin

Chen

Hwu

et al. 2022

IJMS

View full text Add to dashboard Cite

Aptamers are single-stranded, short DNA or RNA oligonucleotides that can specifically bind to various target molecules. To diagnose the infected cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in time, numerous conventional methods are applied for viral detection via the amplification and quantification of DNA or antibodies specific to antigens on the virus. Herein, we generated a large number of mutated aptamer sequences, derived from a known sequence of receptor-binding domain (RBD)-1C aptamer, specific to the RBD of SARS-CoV-2 spike protein (S protein). Structural similarity, molecular docking, and molecular dynamics (MD) were utilized to screen aptamers and characterize the detailed interactions between the selected aptamers and the S protein. We identified two mutated aptamers, namely, RBD-1CM1 and RBD-1CM2, which presented better docking results against the S protein compared with the RBD-1C aptamer. Through the MD simulation, we further confirmed that the RBD-1CM1 aptamer can form the most stable complex with the S protein based on the number of hydrogen bonds formed between the two biomolecules. Based on the experimental data of quartz crystal microbalance (QCM), the RBD-1CM1 aptamer could produce larger signals in mass change and exhibit an improved binding affinity to the S protein. Therefore, the RBD-1CM1 aptamer, which was selected from 1431 mutants, was the best potential candidate for the detection of SARS-CoV-2. The RBD-1CM1 aptamer can be an alternative biological element for the development of SARS-CoV-2 diagnostic testing.

show abstract

“…For instance, Sun, Liu, Song, et al ( 2021 ) demonstrated that aptamer cocktails displayed the higher RBD and pseudovirus neutralizing efficiency compared to their individual aptamer counterparts with the same concentration. In terms of aptamer multimerization, Valero et al ( 2021 ) engineered dimeric and trimeric versions of RBD‐PB6‐Ta aptamers via a scaffolding or poly(A) linkage approach. Compared to the monomeric aptamer, both dimeric and trimeric forms demonstrated an enhanced spike protein binding avidity ( K D values of 0.4 nM, 72 pM, and 39 pM for monomer, dimer, and trimer, respectively) and efficiently neutralized real SARS‐COV‐2 virus with respective IC 50 values of 1.5 μM, 387 nM, and 46 nM.…”

Section: Coronavirus Aptamer Selection Category and Engineeringmentioning

confidence: 99%

Aptamers as promising nanotheranostic tools in the COVID‐19 pandemic era

Dzuvor

Tettey

Danquah

2022

WIREs Nanomed Nanobiotechnol

View full text Add to dashboard Cite

The emergence of SARS‐COV‐2, the causative agent of new coronavirus disease (COVID‐19) has become a pandemic threat. Early and precise detection of the virus is vital for effective diagnosis and treatment. Various testing kits and assays, including nucleic acid detection methods, antigen tests, serological tests, and enzyme‐linked immunosorbent assay (ELISA), have been implemented or are being explored to detect the virus and/or characterize cellular and antibody responses to the infection. However, these approaches have inherent drawbacks such as nonspecificity, high cost, are characterized by long turnaround times for test results, and can be labor‐intensive. Also, the circulating SARS‐COV‐2 variant of concerns, reduced antibody sensitivity and/or neutralization, and possible antibody‐dependent enhancement (ADE) have warranted the search for alternative potent therapeutics. Aptamers, which are single‐stranded oligonucleotides, generated artificially by SELEX (Evolution of Ligands by Exponential Enrichment) may offer the capacity to generate high‐affinity neutralizers and/or bioprobes for monitoring relevant SARS‐COV‐2 and COVID‐19 biomarkers. This article reviews and discusses the prospects of implementing aptamers for rapid point‐of‐care detection and treatment of SARS‐COV‐2. We highlight other SARS‐COV‐2 targets (N protein, spike protein stem‐helix), SELEX augmented with competition assays and in silico technologies for rapid discovery and isolation of theranostic aptamers against COVID‐19 and future pandemics. It further provides an overview on site‐specific bioconjugation approaches, customizable molecular scaffolding strategies, and nanotechnology platforms to engineer these aptamers into ultrapotent blockers, multivalent therapeutics, and vaccines to boost both humoral and cellular immunity against the virus. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > Biosensing Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease

show abstract

A serum-stable RNA aptamer specific for SARS-CoV-2 neutralizes viral entry

Cited by 79 publications

References 61 publications

SCORe: SARS-CoV-2 Omicron Variant RBD-Binding DNA Aptamer for Multiplexed Rapid Detection and Pseudovirus Neutralization

SCORe: SARS-CoV-2 Omicron Variant RBD-Binding DNA Aptamer for Multiplexed Rapid Detection and Pseudovirus Neutralization

In-Silico Selection of Aptamer Targeting SARS-CoV-2 Spike Protein

Aptamers as promising nanotheranostic tools in the COVID‐19 pandemic era

Contact Info

Product

Resources

About