| Autor: |
Jokinen EM, Gopinath K, Kurkinen ST, Pentikainen OT |
| Jazyk: |
angličtina |
| Zdroj: |
IEEE/ACM transactions on computational biology and bioinformatics [IEEE/ACM Trans Comput Biol Bioinform] 2021 Jul-Aug; Vol. 18 (4), pp. 1281-1289. Date of Electronic Publication: 2021 Aug 06. |
| DOI: |
10.1109/TCBB.2021.3076259 |
| Abstrakt: |
The novel SARS-CoV-2 uses ACE2 (Angiotensin-Converting Enzyme 2) receptor as an entry point. Insights on S protein receptor-binding domain (RBD) interaction with ACE2 receptor and drug repurposing has accelerated drug discovery for the novel SARS-CoV-2 infection. Finding small molecule binding sites in S protein and ACE2 interface is crucial in search of effective drugs to prevent viral entry. In this study, we employed molecular dynamics simulations in mixed solvents together with virtual screening to identify small molecules that could be potential inhibitors of S protein -ACE2 interaction. Observation of organic probe molecule localization during the simulations revealed multiple sites at the S protein surface related to small molecule, antibody, and ACE2 binding. In addition, a novel conformation of the S protein was discovered that could be stabilized by small molecules to inhibit attachment to ACE2. The most promising binding site on RBD-ACE2 interface was targeted with virtual screening and top-ranked compounds (DB08248, DB02651, DB03714, and DB14826) are suggested for experimental testing. The protocol described here offers an extremely fast method for characterizing key proteins of a novel pathogen and for the identification of compounds that could inhibit or accelerate spreading of the disease. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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