SELEX based aptamers with diagnostic and entry inhibitor therapeutic potential for SARS-CoV-2.

Autor: Halder S; Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, 835215, India., Thakur A; Department of Chemistry, University of Miami, Coral Gables, FL, 33146, USA., Keshry SS; Institute of Life Sciences, Bhubaneswar, Odisha, 751023, India.; School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT) University, Bhubaneswar, Odisha, India., Jana P; Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, 835215, India., Karothia D; Institute of Life Sciences, Bhubaneswar, Odisha, 751023, India., Das Jana I; School of Bioscience, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, 721302, India., Acevedo O; Department of Chemistry, University of Miami, Coral Gables, FL, 33146, USA., Swain RK; Institute of Life Sciences, Bhubaneswar, Odisha, 751023, India., Mondal A; School of Bioscience, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, 721302, India., Chattopadhyay S; Institute of Life Sciences, Bhubaneswar, Odisha, 751023, India., Jayaprakash V; Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, 835215, India., Dev A; Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, 835215, India. abhimanyudev@bitmesra.ac.in.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Sep 04; Vol. 13 (1), pp. 14560. Date of Electronic Publication: 2023 Sep 04.
DOI: 10.1038/s41598-023-41885-w
Abstrakt: Frequent mutation and variable immunological protection against vaccination is a common feature for COVID-19 pandemic. Early detection and confinement remain key to controlling further spread of infection. In response, we have developed an aptamer-based system that possesses both diagnostic and therapeutic potential towards the virus. A random aptamer library (~ 10 17 molecules) was screened using systematic evolution of ligands by exponential enrichment (SELEX) and aptamer R was identified as a potent binder for the SARS-CoV-2 spike receptor binding domain (RBD) using in vitro binding assay. Using a pseudotyped viral entry assay we have shown that aptamer R specifically inhibited the entry of a SARS-CoV-2 pseudotyped virus in HEK293T-ACE2 cells but did not inhibit the entry of a Vesicular Stomatitis Virus (VSV) glycoprotein (G) pseudotyped virus, hence establishing its specificity towards SARS-CoV-2 spike protein. The antiviral potential of aptamers R and J (same central sequence as R but lacking flanked primer regions) was tested and showed 95.4% and 82.5% inhibition, respectively, against the SARS-CoV-2 virus. Finally, intermolecular interactions between the aptamers and the RBD domain were analyzed using in silico docking and molecular dynamics simulations that provided additional insight into the binding and inhibitory action of aptamers R and J.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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