8J26

CryoEM structure of SARS CoV-2 RBD and Aptamer complex

Summary for 8J26

• Entry DOI: 10.2210/pdb8j26/pdb
• EMDB information: 35945
• Descriptor: AM032-4, Fab light chain (REGN10987), Fab heavy chain (REGN10987), ... (6 entities in total)
• Functional Keywords: aptamer, sars cov-2 rbd, inhibitor, napdu, viral protein, viral protein-immune system-dna complex, viral protein/immune system/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 110986.75

Authors

Rahman, M.S.,Jang, S.K.,Lee, J.O. (deposition date: 2023-04-14, release date: 2023-06-21, Last modification date: 2024-11-20)

Primary citation

Rahman, M.S.,Han, M.J.,Kim, S.W.,Kang, S.M.,Kim, B.R.,Kim, H.,Lee, C.J.,Noh, J.E.,Kim, H.,Lee, J.O.,Jang, S.K.
Structure-Guided Development of Bivalent Aptamers Blocking SARS-CoV-2 Infection.
Molecules, 28:-, 2023

PubMed Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused devastation to human society through its high virulence, infectivity, and genomic mutations, which reduced the efficacy of vaccines. Here, we report the development of aptamers that effectively interfere with SARS-CoV-2 infection by targeting its spike protein, which plays a pivotal role in host cell entry of the virus through interaction with the viral receptor angiotensin-converting enzyme 2 (ACE2). To develop highly effective aptamers and to understand their mechanism in inhibiting viral infection, we determined the three-dimensional (3D) structures of aptamer/receptor-binding domain (RBD) complexes using cryogenic electron microscopy (cryo-EM). Moreover, we developed bivalent aptamers targeting two distinct regions of the RBD in the spike protein that directly interact with ACE2. One aptamer interferes with the binding of ACE2 by blocking the ACE2-binding site in RBD, and the other aptamer allosterically inhibits ACE2 by binding to a distinct face of RBD. Using the 3D structures of aptamer-RBD complexes, we minimized and optimized these aptamers. By combining the optimized aptamers, we developed a bivalent aptamer that showed a stronger inhibitory effect on virus infection than the component aptamers. This study confirms that the structure-based aptamer-design approach has a high potential in developing antiviral drugs against SARS-CoV-2 and other viruses.

PubMed: 37375202
DOI: 10.3390/molecules28124645

Experimental method

ELECTRON MICROSCOPY (3.4 Å)