The Development of Pharmacophore Models for the Search of New Natural Inhibitors of SARS-CoV-2 Spike RBD-ACE2 Binding Interface.
Valentin A SemenovLeonid B KridvinPublished in: Molecules (Basel, Switzerland) (2022)
To date, some succeeding variants of SARS-CoV-2 have become more contagious. This virus is known to enter human cells by binding the receptor-binding domain (RBD) of spike protein with the angiotensin-converting enzyme 2 (ACE2), the latter being a membrane protein that regulates the renin-angiotensin system. Since the host cell receptor plays a critical role in viral entry, inhibition of the RBD-ACE2 complex is a promising strategy for preventing COVID-19 infection. In the present communication, we propose and utilize an approach based on the generation of a complex of pharmacophore models and subsequent Induced Fit Docking (IFD) to identify potential inhibitors of the main binding sites of the Omicron SARS-CoV-2 RBD(S1)-ACE2 complex (PDB ID: 7T9L) among a number of natural products of various types and origins. Several natural compounds have been found to provide a high affinity for the receptor of interest. It is expected that the present results will stimulate further research aimed at the development of specialized drugs against this virus.
Keyphrases
- angiotensin converting enzyme
- sars cov
- angiotensin ii
- binding protein
- respiratory syndrome coronavirus
- molecular dynamics
- molecular docking
- dna binding
- protein protein
- palliative care
- single cell
- molecular dynamics simulations
- high glucose
- cell therapy
- gene expression
- small molecule
- coronavirus disease
- transcription factor
- climate change
- bone marrow
- disease virus