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Different compounds against Angiotensin-Converting Enzyme 2 (ACE2) receptor potentially containing the infectivity of SARS-CoV-2: an in silico study.
J Mol Model. 2022 Mar 05; 28(4):82.JM

Abstract

Novel SARS coronavirus or SARS-CoV-2 is a novel coronavirus that was identified and spread from Wuhan in 2019. On January 30th, the World Health Organization declared the coronavirus outbreak as a Global Public Health Emergency. Although Remdesivir and Molnupiravir are FDA-approved drugs for COVID-19, finding new efficient and low-cost antiviral drugs against COVID-19 for applying in more countries can still be helpful. One of the potential sources for finding new and low-cost drugs is the herbal compounds in addition to repurposing FDA-approved drugs. So, in this study, we focused on finding effective drug candidates against COVID-19 based on the computational approaches. As ACE2 serves as a critical receptor for cell entry of this virus. Inhibiting the binding site of SARS-CoV-2 on human ACE2 provides a promising therapeutic approach for developing drugs against SARS-CoV-2. Herein, we applied a bioinformatics approach to identify possible potential inhibitors of SARS-CoV-2. A library of FDA-approved compounds and five natural compounds was screened using Smina docking. Top-docking compounds are then applied in Molecular Dynamics (MD) simulation to assess the stability of ACE2-inhibitor complexes. Results indicate that Luteolin and Chrysin represent high conformation stability with ACE2 during 120 ns of Molecular Dynamics simulation. The binding free energies of Luteolin and Chrysin were calculated by the Molecular Mechanics/Poisson-Boltzmann Surface Area method (MM/PBSA) which confirmed the relative binding free energy of these drugs to ACE2 in favor of the effective binding. So, Luteolin and Chrysin could sufficiently interact with ACE2 and block the Spike binding pocket of ACE2 and can be a potential inhibitor against the binding of SARS-CoV-2 to ACE2 receptor which is an early stage of infection. Luteolin and Chrysin could be suggestive as beneficial compounds for preventing or reducing SARS-CoV-2 transmission and infection which need experimental work to prove.

Authors+Show Affiliations

Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, 69th Pasteur Street, Kargar Avenue, Tehran, Iran.Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, 69th Pasteur Street, Kargar Avenue, Tehran, Iran.Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, 69th Pasteur Street, Kargar Avenue, Tehran, Iran. lteimoori@pasteur.ac.ir.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

35249180

Citation

Shahbazi, Behzad, et al. "Different Compounds Against Angiotensin-Converting Enzyme 2 (ACE2) Receptor Potentially Containing the Infectivity of SARS-CoV-2: an in Silico Study." Journal of Molecular Modeling, vol. 28, no. 4, 2022, p. 82.
Shahbazi B, Mafakher L, Teimoori-Toolabi L. Different compounds against Angiotensin-Converting Enzyme 2 (ACE2) receptor potentially containing the infectivity of SARS-CoV-2: an in silico study. J Mol Model. 2022;28(4):82.
Shahbazi, B., Mafakher, L., & Teimoori-Toolabi, L. (2022). Different compounds against Angiotensin-Converting Enzyme 2 (ACE2) receptor potentially containing the infectivity of SARS-CoV-2: an in silico study. Journal of Molecular Modeling, 28(4), 82. https://doi.org/10.1007/s00894-022-05059-1
Shahbazi B, Mafakher L, Teimoori-Toolabi L. Different Compounds Against Angiotensin-Converting Enzyme 2 (ACE2) Receptor Potentially Containing the Infectivity of SARS-CoV-2: an in Silico Study. J Mol Model. 2022 Mar 5;28(4):82. PubMed PMID: 35249180.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Different compounds against Angiotensin-Converting Enzyme 2 (ACE2) receptor potentially containing the infectivity of SARS-CoV-2: an in silico study. AU - Shahbazi,Behzad, AU - Mafakher,Ladan, AU - Teimoori-Toolabi,Ladan, Y1 - 2022/03/05/ PY - 2021/05/02/received PY - 2022/02/15/accepted PY - 2022/3/6/entrez PY - 2022/3/7/pubmed PY - 2022/3/11/medline KW - Angiotensin-converting enzyme 2 KW - Chrysin KW - Luteolin KW - Molecular Docking Simulation KW - Molecular Dynamics simulation KW - SARS-CoV-2 KW - Spike protein SP - 82 EP - 82 JF - Journal of molecular modeling JO - J Mol Model VL - 28 IS - 4 N2 - Novel SARS coronavirus or SARS-CoV-2 is a novel coronavirus that was identified and spread from Wuhan in 2019. On January 30th, the World Health Organization declared the coronavirus outbreak as a Global Public Health Emergency. Although Remdesivir and Molnupiravir are FDA-approved drugs for COVID-19, finding new efficient and low-cost antiviral drugs against COVID-19 for applying in more countries can still be helpful. One of the potential sources for finding new and low-cost drugs is the herbal compounds in addition to repurposing FDA-approved drugs. So, in this study, we focused on finding effective drug candidates against COVID-19 based on the computational approaches. As ACE2 serves as a critical receptor for cell entry of this virus. Inhibiting the binding site of SARS-CoV-2 on human ACE2 provides a promising therapeutic approach for developing drugs against SARS-CoV-2. Herein, we applied a bioinformatics approach to identify possible potential inhibitors of SARS-CoV-2. A library of FDA-approved compounds and five natural compounds was screened using Smina docking. Top-docking compounds are then applied in Molecular Dynamics (MD) simulation to assess the stability of ACE2-inhibitor complexes. Results indicate that Luteolin and Chrysin represent high conformation stability with ACE2 during 120 ns of Molecular Dynamics simulation. The binding free energies of Luteolin and Chrysin were calculated by the Molecular Mechanics/Poisson-Boltzmann Surface Area method (MM/PBSA) which confirmed the relative binding free energy of these drugs to ACE2 in favor of the effective binding. So, Luteolin and Chrysin could sufficiently interact with ACE2 and block the Spike binding pocket of ACE2 and can be a potential inhibitor against the binding of SARS-CoV-2 to ACE2 receptor which is an early stage of infection. Luteolin and Chrysin could be suggestive as beneficial compounds for preventing or reducing SARS-CoV-2 transmission and infection which need experimental work to prove. SN - 0948-5023 UR - https://www.unboundmedicine.com/medline/citation/35249180/Different_compounds_against_Angiotensin_Converting_Enzyme_2__ACE2__receptor_potentially_containing_the_infectivity_of_SARS_CoV_2:_an_in_silico_study_ L2 - https://dx.doi.org/10.1007/s00894-022-05059-1 DB - PRIME DP - Unbound Medicine ER -