tetano
Editor, Senior Moderator
J Mol Graph Model
. 2022 Apr 27;114:108206.
doi: 10.1016/j.jmgm.2022.108206. Online ahead of print.
Virtual and biochemical screening to identify the inhibitors of binding between SARS-CoV-2 spike protein and human angiotensin-converting enzyme 2
Chanyoub Park[SUP] 1 [/SUP], Changsun Eun[SUP] 2 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV-2) appeared as a new viral pathogen and caused the COVID-19 pandemic worldwide. Since the antiviral medicines effective for the treatment of COVID-19 are rare, it is necessary to identify the new candidate molecules for chemotherapy. The glycosylated Spike protein (S-protein) of SARS-CoV-2 plays a critical role in entering into the host cell through a direct interaction with human angiotensin-converting enzyme 2 (ACE2). For this reason, S-protein has served as one of the most effective therapeutic targets for discovering the antiviral medicines for COVID-19. In this work, we report the new small-molecule inhibitors of the interaction between the S-protein of SARS-CoV-2 and human ACE2, which were discovered through the structure-based virtual screening and in vitro biochemical binding assays. As a consequence of combining the computational and experimental validations, three novel inhibitors against the binding of S-protein and ACE2 were found with the associated IC[SUB]50[/SUB] values ranging from 50 to 100 μM. Although the biochemical potencies are moderate, the newly found inhibitors are worth being considered for further investigation by structure-activity relationship analysis to maximize the antiviral activity because of the low molecular weights and good physicochemical properties as a drug candidate. The interaction patterns of the new inhibitors in the ACE2-binding region of S-protein are addressed in detail.
Keywords: ACE2; Antiviral agents; COVID-19; Spike protein; Virtual screening.
. 2022 Apr 27;114:108206.
doi: 10.1016/j.jmgm.2022.108206. Online ahead of print.
Virtual and biochemical screening to identify the inhibitors of binding between SARS-CoV-2 spike protein and human angiotensin-converting enzyme 2
Chanyoub Park[SUP] 1 [/SUP], Changsun Eun[SUP] 2 [/SUP]
Affiliations
- PMID: 35504156
- DOI: 10.1016/j.jmgm.2022.108206
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV-2) appeared as a new viral pathogen and caused the COVID-19 pandemic worldwide. Since the antiviral medicines effective for the treatment of COVID-19 are rare, it is necessary to identify the new candidate molecules for chemotherapy. The glycosylated Spike protein (S-protein) of SARS-CoV-2 plays a critical role in entering into the host cell through a direct interaction with human angiotensin-converting enzyme 2 (ACE2). For this reason, S-protein has served as one of the most effective therapeutic targets for discovering the antiviral medicines for COVID-19. In this work, we report the new small-molecule inhibitors of the interaction between the S-protein of SARS-CoV-2 and human ACE2, which were discovered through the structure-based virtual screening and in vitro biochemical binding assays. As a consequence of combining the computational and experimental validations, three novel inhibitors against the binding of S-protein and ACE2 were found with the associated IC[SUB]50[/SUB] values ranging from 50 to 100 μM. Although the biochemical potencies are moderate, the newly found inhibitors are worth being considered for further investigation by structure-activity relationship analysis to maximize the antiviral activity because of the low molecular weights and good physicochemical properties as a drug candidate. The interaction patterns of the new inhibitors in the ACE2-binding region of S-protein are addressed in detail.
Keywords: ACE2; Antiviral agents; COVID-19; Spike protein; Virtual screening.