Virtual and biochemical screening to identify the inhibitors of binding between SARS-CoV-2 spike protein and human angiotensin-converting enzyme 2

Park, Chanyoub; Eun, Changsun

doi:10.1016/j.jmgm.2022.108206

Cited by 2 publications

(2 citation statements)

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“…In the effort to design small molecule drug against SARS-CoV-2 and its spreading variants, various potential chemical compounds have been reported, having scaffold including; oxazole-carboxamides, benzamides, anthraquinone, piperidine, alkylamines, triazole, benzimidazole, carbasugars, Methylene Blue derivatives, phenolic derivatives), flavanone, and others [ 41 , 42 , 43 , 44 ]. The five selected virtual hits: AKS-01 (unpublished), AKS-02 [ 45 ], AKS-03 (unpublished) AKS-04 (unpublished), and AKS-05 [ 46 ], belong to the chemical class benzamide, benzothiazine, triazole, benzimidazole, and thiazol, respectively, and were previously synthesized by a synthetic group from our institute.…”

Section: Resultsmentioning

confidence: 99%

“…π-cation interaction was also observed with Arg403. Recently, Park and Eun reported the in vitro studies of some chemical compounds having a benzimidazole scaffold using the binding bioassay between Spike protein and human ACE2 receptor [ 43 ]. The study suggested that benzimidazole is an attractive scaffold for further development as a SARS-CoV-2 entry inhibitor.…”

Section: Resultsmentioning

confidence: 99%

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Cheminformatics-Based Discovery of Potential Chemical Probe Inhibitors of Omicron Spike Protein

Khan

Zia

et al. 2022

IJMS

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During the past two decades, the world has witnessed the emergence of various SARS-CoV-2 variants with distinct mutational profiles influencing the global health, economy, and clinical aspects of the COVID-19 pandemic. These variants or mutants have raised major concerns regarding the protection provided by neutralizing monoclonal antibodies and vaccination, rates of virus transmission, and/or the risk of reinfection. The newly emerged Omicron, a genetically distinct lineage of SARS-CoV-2, continues its spread in the face of rising vaccine-induced immunity while maintaining its replication fitness. Efforts have been made to improve the therapeutic interventions and the FDA has issued Emergency Use Authorization for a few monoclonal antibodies and drug treatments for COVID-19. However, the current situation of rapidly spreading Omicron and its lineages demands the need for effective therapeutic interventions to reduce the COVID-19 pandemic. Several experimental studies have indicated that the FDA-approved monoclonal antibodies are less effective than antiviral drugs against the Omicron variant. Thus, in this study, we aim to identify antiviral compounds against the Spike protein of Omicron, which binds to the human angiotensin-converting enzyme 2 (ACE2) receptor and facilitates virus invasion. Initially, docking-based virtual screening of the in-house database was performed to extract the potential hit compounds against the Spike protein. The obtained hits were optimized by DFT calculations to determine the electronic properties and molecular reactivity of the compounds. Further, MD simulation studies were carried out to evaluate the dynamics of protein–ligand interactions at an atomistic level in a time-dependent manner. Collectively, five compounds (AKS-01, AKS-02, AKS-03, AKS-04, and AKS-05) with diverse scaffolds were identified as potential hits against the Spike protein of Omicron. Our study paves the way for further in vitro and in vivo studies.

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