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In Silico Discovering STRA 6 Vitamin A Receptor, as a Novel Binding Receptor of COVID-19

Elkazzaz et al., Indian Journal of Pharmaceutical Education and Research, doi:10.5530/ijper.57.4.126
Oct 2023  
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Vitamin A for COVID-19
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In Silico study analyzing the potential role of the STRA6 vitamin A receptor in SARS-CoV-2 infection. Authors found that the SARS-CoV-2 spike protein binds strongly to STRA6, suggesting potential use in addition to ACE2. Binding to STRA6 could disrupt vitamin A uptake and explain some COVID-19 complications like immune suppression. The authors propose restoring balance between STRA6 and ACE2 as a promising therapeutic target.
10 preclinical studies support the efficacy of vitamin A for COVID-19:
Vitamin A has been identified by the European Food Safety Authority (EFSA) as having sufficient evidence for a causal relationship between intake and optimal immune system function10-12. Vitamin A has potent antiviral activity against SARS-CoV-2 in both human cell lines and human organoids of the lower respiratory tract (active metabolite all-trans retinoic acid, ATRA)7, is predicted to bind critical host and viral proteins for SARS-CoV-2 and may compensate for gene expression changes related to SARS-CoV-21-3, may be beneficial for COVID-19 via antiviral, anti-inflammatory, and immunomodulatory effects according to network pharmacology analysis4, reduces barrier compromise caused by TNF-α in Calu-3 cells6, inhibits mouse coronavirus replication9, may stimulate innate immunity by activating interferon responses in an IRF3-dependent manner (ATRA)9, may reduce excessive inflammation induced by SARS-CoV-21, shows SARS-CoV-2 antiviral activity In Vitro1,5,8, is effective against multiple SARS-CoV-2 variants in Calu-3 cells8, and inhibits the entry and replication of SARS-CoV-2 via binding to ACE2 / 3CLpro / RdRp / helicase / 3′-to-5′ exonuclease1.
Elkazzaz et al., 4 Oct 2023, peer-reviewed, 15 authors. Contact:
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperVitamin AAll
In silico Discovering STRA 6 Vitamin A Receptor, as a Novel Binding Receptor of COVID-19
Mahmoud Elkazzaz, Amr Ahmed, Yousry Esam Eldin Abo Amer, Tamer Haydara, Wafa Ali Eltayb, Mohammad Shahbaz Khan, Kunal Bhattacharya, Salma Alkhammash, Hadeer Mattar, Saba Beigh, Mohammed F Abo El Magd, Abdullah Haikal, Islem Abid, Amr S Abouzied, Dr Israa M Shamkh
Indian Journal of Pharmaceutical Education and Research, doi:10.5530/ijper.57.4.126
A global pandemic of pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, at the end of 2019. Although, the ACE2 receptor has been demonstrated to be the main entry receptor of COVID-19, but our docking analysis, predicted and discovered a novel receptor termed STRA 6 that may play a critical role in the pathogenicity of COVID-19. STRA6 receptor expressed in many organs and immune cells, upregulated by retinoic acid jm6 (STRA 6) was the first protein to be identified in a novel category of proteins, cytokine signaling transporters, due to its ability to function as both a cell surface receptor and a membrane protein that binds to retinol binding protein facilitating cellular uptake of retinol. The primary ligand of STRA6 (vitamin/retinol) was shown to be drastically reduced during COVID-19 infection, which agrees with our findings. We analyze the STRA6 and ACE2 receptor networks to predict the specific association among certain other proteins which might rely on similar functionality. Molecular docking showed a high affinity between the Spike protein with STRA6, the docking score of COVID-19 spike protein with STRA6 (-354.68) kcal/mol was higher than the docking score of spike protein with ACE2 (-341.21) kcal/mol. Results of MD simulations revealed significant stability of the spike protein with STRA6 up to 100 ns. SARS-CoV-2 spike protein binds strongly and directly to STRA6. Which are highly expressed in Lymphatic system and Immune cells. This study paves the way towards understanding the complex mechanism of existing of covid-19 infection complications such as immune suppression and ineffective RIG-I pathway. Restoring the balance between the STRA6 and ACE2 in the context of spike protein RBD may be promising target in SARS CoV-2 Pathogenesis and may reveal new drug targets for new variants of COVID-19.
ACKNOWLEDGEMENT The authors extend their appreciation to the Researchers Supporting Project number (RSPD2023R745), King Saud University, Riyadh, Saudi Arabia. CONFLICT OF INTEREST The authors declare that there is no conflict of interest. AUTHORS' CONTRIBUTIONS Mahmoud Elkazzaz, Israa M. Shamkh and Amr Ahmed: Conceptualization Mahmoud Elkazzaz, Israa M. Shamkh, Amr Ahmed, Abdullah Haikal, data curation, formal analysis, investigation, methodology, software, validation, visualization, writing -original draft, writing -review, editing, validation, visualization, writing -original draft, writing -review and editing.
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