tetano
Editor, Senior Moderator
Heliyon
. 2021 Mar;7(3):e06515.
doi: 10.1016/j.heliyon.2021.e06515. Epub 2021 Mar 14.
Evaluation of flavonoids as 2019-nCoV cell entry inhibitor through molecular docking and pharmacological analysis
Deep Bhowmik[SUP] 1 [/SUP], Rajat Nandi[SUP] 1 [/SUP], Amresh Prakash[SUP] 2 [/SUP], Diwakar Kumar[SUP] 1 [/SUP]
Affiliations
Abstract
The outbreak of Coronavirus Disease 2019 (COVID-19) has been declared as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO), which is being rapidly spread by the extremely spreadable and pathogenic 2019 novel coronavirus (2019-nCoV), also known as SARS-CoV-2. Pandemic incidence of COVID-19 has created a severe threat to global public health, necessitating the development of effective drugs or inhibitors or therapeutics agents against SARS-CoV-2. Spike protein (S) of the SARS-CoV-2 plays a crucial role in entering viruses into the host cell by binding to angiotensin-converting enzyme 2 (ACE-2), and this specific interaction represents a promising drug target for the identification of potential drugs. This study aimed at the receptor-binding domain of S protein (RBD of nCoV-SP) and the ACE-2 receptor as a promising target for developing drugs against SARS-CoV-2. Over 100 different flavonoids with antioxidant, anti-inflammatory, and antiviral properties from different literatures were taken as a ligand or inhibitor for molecular docking against target protein RBD of nCoV-SP and ACE-2 using PyRX and iGEMDOCK. Top flavonoids based on docking scores were selected for the pharmacokinetic study. Selected flavonoids (hesperidin, naringin, ECGC, and quercetin) showed excellent pharmacokinetics with proper absorption, solubility, permeability, distribution, metabolism, minimal toxicity, and excellent bioavailability. Molecular dynamics simulation studies up to 100 ns exhibited strong binding affinity of selected flavonoids to RBD of nCoV-SP and ACE-2, and the protein-ligand complexes were structurally stable. These identified lead flavonoids may act as potential compounds for developing effective drugs against SARS-CoV-2 by potentially inhibiting virus entry into the host cell.
Keywords: ADMET; Angiotensin-converting enzyme- 2; COVID-19; Flavonoids; Molecular docking; S-glycoprotein RBD; SARS-CoV-2.
. 2021 Mar;7(3):e06515.
doi: 10.1016/j.heliyon.2021.e06515. Epub 2021 Mar 14.
Evaluation of flavonoids as 2019-nCoV cell entry inhibitor through molecular docking and pharmacological analysis
Deep Bhowmik[SUP] 1 [/SUP], Rajat Nandi[SUP] 1 [/SUP], Amresh Prakash[SUP] 2 [/SUP], Diwakar Kumar[SUP] 1 [/SUP]
Affiliations
- PMID: 33748510
- PMCID: PMC7955945
- DOI: 10.1016/j.heliyon.2021.e06515
Abstract
The outbreak of Coronavirus Disease 2019 (COVID-19) has been declared as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO), which is being rapidly spread by the extremely spreadable and pathogenic 2019 novel coronavirus (2019-nCoV), also known as SARS-CoV-2. Pandemic incidence of COVID-19 has created a severe threat to global public health, necessitating the development of effective drugs or inhibitors or therapeutics agents against SARS-CoV-2. Spike protein (S) of the SARS-CoV-2 plays a crucial role in entering viruses into the host cell by binding to angiotensin-converting enzyme 2 (ACE-2), and this specific interaction represents a promising drug target for the identification of potential drugs. This study aimed at the receptor-binding domain of S protein (RBD of nCoV-SP) and the ACE-2 receptor as a promising target for developing drugs against SARS-CoV-2. Over 100 different flavonoids with antioxidant, anti-inflammatory, and antiviral properties from different literatures were taken as a ligand or inhibitor for molecular docking against target protein RBD of nCoV-SP and ACE-2 using PyRX and iGEMDOCK. Top flavonoids based on docking scores were selected for the pharmacokinetic study. Selected flavonoids (hesperidin, naringin, ECGC, and quercetin) showed excellent pharmacokinetics with proper absorption, solubility, permeability, distribution, metabolism, minimal toxicity, and excellent bioavailability. Molecular dynamics simulation studies up to 100 ns exhibited strong binding affinity of selected flavonoids to RBD of nCoV-SP and ACE-2, and the protein-ligand complexes were structurally stable. These identified lead flavonoids may act as potential compounds for developing effective drugs against SARS-CoV-2 by potentially inhibiting virus entry into the host cell.
Keywords: ADMET; Angiotensin-converting enzyme- 2; COVID-19; Flavonoids; Molecular docking; S-glycoprotein RBD; SARS-CoV-2.