Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jun;39(9):3194-3203.
doi: 10.1080/07391102.2020.1761881. Epub 2020 May 5.

Natural products may interfere with SARS-CoV-2 attachment to the host cell

Abdo A Elfiky  1
Affiliations

Natural products may interfere with SARS-CoV-2 attachment to the host cell

Abdo A Elfiky. J Biomol Struct Dyn. 2021 Jun.

Abstract

SARS-CoV-2 has been emerged in December 2019 in China, causing deadly (5% mortality) pandemic pneumonia, termed COVID-19. More than one host-cell receptor is reported to be recognized by the viral spike protein, among them is the cell-surface Heat Shock Protein A5 (HSPA5), also termed GRP78 or BiP. Upon viral infection, HSPA5 is upregulated, then translocating to the cell membrane where it is subjected to be recognized by the SARS-CoV-2 spike. In this study, some natural product compounds are tested against the HSPA5 substrate-binding domain β (SBDβ), which reported to be the recognition site for the SARS-CoV-2 spike. Molecular docking and molecular dynamics simulations are used to test some natural compounds binding to HSPA5 SBDβ. The results show high to a moderate binding affinity for the phytoestrogens (Diadiazin, Genistein, Formontein, and Biochanin A), chlorogenic acid, linolenic acid, palmitic acid, caffeic acid, caffeic acid phenethyl ester, hydroxytyrosol, cis-p-Coumaric acid, cinnamaldehyde, thymoquinone, and some physiological hormones such as estrogens, progesterone, testosterone, and cholesterol to the HSPA5 SBDβ. Based on its binding affinities, the phytoestrogens and estrogens are the best in binding HSPA5, hence may interfere with SARS-CoV-2 attachment to the stressed cells. These compounds can be successful as anti-COVID-19 agents for people with a high risk of cell stress like elders, cancer patients, and front-line medical staff.Communicated by Ramaswamy H. Sarma.

Keywords: COVID-19; GRP78; HSPA5; molecular dynamics simulation; natural compounds; peptide-protein docking.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
2 D structures of the natural product derived compounds (A) and physiological compounds (B).
Figure 2.
Figure 2.
(A) Root Mean Square Deviation (RMSD) in Å (blue line), Radius of Gyration (RoG) in Å (orange line), and Surface Accessible Surface Area (SASA) in Å2 (gray line) versus time in ns for HSPA5. MDS is performed using CHARMM 36 force field by NAMD. (B) per residue, Root Mean Square Fluctuations (RMSF) in Å (blue line). The structure of HSPA5 is shown in the colored carton with its domain labeled NBD (nucleotide-binding domain) SBD (substrate-binding domains). Blue and red balls, respectively represent N and C terminals of the protein. SBDβ is depicted in cyan cartoon and indicated in the RMSF histogram, while the most movable internal region of HSPA5 (S540-D583) is represented in the orange cartoon.
Figure 3.
Figure 3.
The average binding affinity (in kcal/mol) calculated using AutoDock Vina software for the docking of the natural products bioactive compounds (A) and physiological compounds (B) into the four different conformations of the HSPA5 SBDβ. The cyclic peptide Pep42 (red column) is used as a reference due to its specificity in binding HSPA5 in vivo. Estrogens and phytoestrogen are among the best binders to HSPA5 SBDβ.
Figure 4.
Figure 4.
The structure of the docked complexes of HSPA5 and the small molecules (A) estradiol, (B) daidzein, and (C) biochanin A. HSPA5 is represented in the colored surface while the docked small molecules are in orange sticks. The NBD, SBDα, and SBDβ domains of the HSPA5 are labeled, while the enlarged panels show the interactions that established upon docking. The active site residues in the expanded panels are marked with its one-letter code and represented in blue sticks. H-bonds, hydrophobic contacts, and π-stacking interactions are shown by blue lines, dashed-gray lines, and dashed-green lines, respectively. The docking score (in kcal/mol) is shown for each complex.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Al-Hashimi A. A., Rak J., & Austin R. C. (2018). Cell surface GRP78: A novel regulator of tissue factor procoagulant activity In Cell surface GRP78, a new paradigm in signal transduction biology (pp. 63–85). England: Elsevier.
    1. Belouzard S., Millet J. K., Licitra B. N., & Whittaker G. R. (2012). Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses, 4(6), 1011–1033. 10.3390/v4061011 - DOI - PMC - PubMed
    1. Biasini M., Bienert S., Waterhouse A., Arnold K., Studer G., Schmidt T., Kiefer F., Cassarino T. G., Bertoni M., Bordoli L., & Schwede T. (2014). SWISS-MODEL: Modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Research, 42(W1), W252–W258. 10.1093/nar/gku340 - DOI - PMC - PubMed
    1. Bogoch I. I., Watts A., Thomas-Bachli A., Huber C., Kraemer M. U. G., & Khan K. (2020). Pneumonia of unknown etiology in Wuhan, China: Potential for international spread via commercial air travel. Journal of Travel Medicine, 27(2), 1-3. 10.1093/jtm/taaa008 - DOI - PMC - PubMed
    1. Bouhlel A., Ben Mosbah I., Hadj Abdallah N., Ribault C., Viel R., Mannaï S., Corlu A., & Ben Abdennebi H. (2017). Thymoquinone prevents endoplasmic reticulum stress and mitochondria-induced apoptosis in a rat model of partial hepatic warm ischemia reperfusion. Biomedicine & Pharmacotherapy, 94, 964–973. 10.1016/j.biopha.2017.08.018 - DOI - PubMed

Substances

-