Review Article
Volume 12 Issue 2 - 2021
Association of Vitamin-D and VDR with ACE2 Modulates the Severity in COVID-19
Muralidharan Jothimani1, Mehboobali Pannipara2,3, Abdullah G Al-Sehemi2,3 and Karthikeyan Muthusamy1*
1Pharmacogenomics and CADD Laboratory, Department of Bioinformatics, Science Block, Alagappa University, Karaikudi, Tamil Nadu, India
2Research center for Advanced Materials Science, King Khalid University, Abha, Saudi Arabia
3Department of Chemistry, King Khalid University, Abha, Saudi Arabia
*Corresponding Author: Karthikeyan Muthusamy, Assistant Professor, Pharmacogenomics and CADD Laboratory, Department of Bioinformatics, Science Block, Alagappa University, Karaikudi, Tamil Nadu, India.
Received: December 23, 2020; Published: January 29, 2021




Abstract

The corona virus disease (COVID-19), lethal to the human population is easily transmitted from one person to another. The major causative agents of novel corona virus (nCoV) are severe acute respiratory syndrome corona virus disease-2 (SARS-CoV-2) and the Middle East Respiratory Syndrome corona virus disease (MERS-CoV). Both novel strains are similar in their pathogenesis and at severity, the condition leads to death. In COVID-19, mortality is strongly associated with humans suffering from diabetes cardiovascular disease and hypertension. The COVID-19 with its spike protein mediates with the Angiotensin-converting enzyme-2 (ACE2) receptor to enter inside the body. The spike glycoprotein binds to ACE2 may be a potent target for developing new specific drugs, antibiotics, repurposed drugs and vaccines. The balancing between ACE2 and Renin-angiotensin system (RAS) aid to reduce the multi-organs injury occurred by COVID-19 and at another criterion, the misbalancing condition between ACE2 and RAS leads to multi-organ damage. The polymorphism in ACE2 is liable to provide the prognostic effects on COVID-19 regulations. Vitamin-D binds with Vitamin-D receptor (VDR) to regulate the gene expression and affects cell proliferation, differentiation; apoptosis and tumor-genesis. VDR as a supplemental factor reduces the severity of various diseases and acts as a multi-targeted gene for various diseases. Vitamin-D and VDR down-regulates the expression of ACE2 and decreases the risk of COVID-19 infection. Targeting Vitamin-D and VDR against COVID-19 may be a potential therapeutic approach for reducing the severity. VDR activation therapeutically targets and potential for Acute Respiratory Distress Syndrome (ARDS), Acute lungs injury (ALI) and Acute- lower respiratory infection (ALRI) diseases. This mini-review discusses the role of ACE2 in COVID-19, targeted with Vitamin-D and VDR to reduce the severity of viral pathogenesis. Targeting with Vitamin-D and VDR directly down-regulates the action of ACE2 receptor, thereby developing a drug, vaccine or antibiotics might be a potent option to decreases the risk of COVID-19 infection. By the shreds of evidence acquired, Vitamin-D and VDR may be the potential therapeutic option for targeting COVID-19.

Keywords: COVID-19; SARS-CoV-2; ACE2; Vitamin-D; VDR

References

  1. Gonzalez JM., et al. "A comparative sequence analysis to revise the current taxonomy of the family Coronaviridae”. Archives of Virology11 (2003): 2207-2235.
  2. Morawska Lidia., et al. "How can airborne transmission of COVID-19 indoors be minimised?”. Environment International 142 (2020): 105832.
  3. Ding Siyuan and T Jake Liang. "Is SARS-CoV-2 also an enteric pathogen with potential Fecal-Oral transmission: a COVID-19 virological and clinical review”. Gastroenterology (2020).
  4. Carfì Angelo., et al. "Persistent symptoms in patients after acute COVID-19”. JAMA6 (2020): 603-605.
  5. World Health Organization. “Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected: interim guidance, 13 March 2020. No. WHO/2019-nCoV/clinical/2020.4. World Health Organization (2020).
  6. Tripp Ralph A and S Mark Tompkins. “Roles of Host Gene and Non-coding RNA Expression in Virus Infection 419 (2018).
  7. Malek Mahdavi Aida. "A brief review of interplay between vitamin D and angiotensin‐converting enzyme 2: Implications for a potential treatment for COVID‐19”. Reviews in Medical Virology5 (2020): e2119.
  8. Zheng Ying-Ying., et al. "COVID-19 and the cardiovascular system”. Nature Reviews Cardiology5 (2020): 259-260.
  9. Behl Tapan., et al. "The dual impact of ACE2 in COVID-19 and ironical actions in geriatrics and pediatrics with possible therapeutic solutions”. Life Sciences (2020): 118075.
  10. Holick Michael F. "Vitamin D deficiency”. New England Journal of Medicine3 (2007): 266-281.
  11. Lips Paul and Natasja M Van Schoor. "The effect of vitamin D on bone and osteoporosis”. Best Practice and Research Clinical Endocrinology and Metabolism4 (2011): 585-591.
  12. Ginde Adit A., et al. "Vitamin D, respiratory infections, and asthma”. Current Allergy and Asthma Reports1 (2009): 81-87.
  13. Meltzer David O., et al. "Association of vitamin D status and other clinical characteristics with COVID-19 test results”. JAMA Network Open9 (2020): e2019722-e2019722.
  14. Maghbooli Zhila., et al. "Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection”. PloS one9 (2020): e0239799.
  15. Alberca Ricardo Wesley., et al. "Obesity as a risk factor for COVID-19: an overview”. Critical Reviews in Food Science and Nutrition (2020): 1-15.
  16. Lester JC., et al. "Absence of Skin of Colour Images in Publications of COVID‐19 Skin Manifestations”. British Journal of Dermatology (2020).
  17. Nagamani Selvaraman., et al. "Atom-based and Pharmacophore-based 3D–QSAR Studies on Vitamin D Receptor (VDR)”. Combinatorial Chemistry and High Throughput Screening 5 (2018): 329-343.
  18. Nagamani Selvaraman., et al. "E-Pharmacophore mapping and docking studies on Vitamin D receptor (VDR)”. Bioinformation15 (2012): 705.
  19. Selvaraman Nagamani., et al. "The binding mode prediction and similar ligand potency in the active site of vitamin D receptor with QM/MM interaction, MESP, and MD simulation”. Chemical Biology and Drug Design 2 (2016): 272-280.
  20. Ebadi Maryam and Aldo J Montano-Loza. "Perspective: improving vitamin D status in the management of COVID-19”. European Journal of Clinical Nutrition (2020): 1-4.
  21. Deeb Kristin K., et al. "Vitamin D signalling pathways in cancer: potential for anticancer therapeutics”. Nature Reviews Cancer9 (2007): 684-700.
  22. Zhang Liang., et al. "Associations between VDR gene polymorphisms and osteoporosis risk and bone mineral density in postmenopausal women: a systematic review and meta-analysis”. Scientific Reports1 (2018): 1-16.
  23. Nagamani Selvaraman., et al. "Combined sequence and sequence-structure based methods for analyzing FGF23, CYP24A1 and VDR genes”. Meta Gene 9 (2016): 26-36.
  24. Jayaraj John Marshal., et al. "In silico identification and screening of CYP24A1 inhibitors: 3D QSAR pharmacophore mapping and molecular dynamics analysis”. Journal of Biomolecular Structure and Dynamics7 (2019): 1700-1714.
  25. Nagamani Selvaraman and Karthikeyan Muthusamy. "A theoretical insight to understand the molecular mechanism of dual target ligand CTA-018 in the chronic kidney disease pathogenesis”. PloS one10 (2018): e0203194.
  26. Jayaraj John Marshal., et al. "Structural insights on Vitamin D receptor and screening of new potent agonist molecules: Structure and ligand-based approach”. Journal of Biomolecular Structure and Dynamics (2020): 1-20.
  27. Torres Armando., et al. "Treatment with intermittent calcitriol and calcium reduces bone loss after renal transplantation”. Kidney International2 (2004): 705-712.
  28. Al-Daghri Nasser M., et al. "Association of VDR-gene variants with factors related to the metabolic syndrome, type 2 diabetes and vitamin D deficiency”. Gene2 (2014): 129-133.
  29. Székely Joseph I and Ágnes Pataki. "Effects of vitamin D on immune disorders with special regard to asthma, COPD and autoimmune diseases: a short review”. Expert Review of Respiratory Medicine6 (2012): 683-704.
  30. Sakharkar Prashant., et al. "Vitamin D Receptor (VDR) gene polymorphism: Implications on non-bone diseases”. Journal of Basic and Clinical Pharmacy 8 (2017): S06-S10.
  31. Zaim Sevim., et al. "COVID-19 and multi-organ response”. Current Problems in Cardiology (2020): 100618.
  32. Xu Jiaxi and Eric Lazartigues. "Expression of ACE2 in human neurons supports the neuro-invasive potential of COVID-19 virus”. Cellular and Molecular Neurobiology (2020): 1-5.
  33. Shenoy Vinayak., et al. "ACE2, a promising therapeutic target for pulmonary hypertension”. Current Opinion in Pharmacology2 (2011): 150-155.
  34. Wicik Zofia., et al. "ACE2 interaction networks in COVID-19: a physiological framework for prediction of outcome in patients with cardiovascular risk factors”. Journal of Clinical Medicine11 (2020): 3743.
  35. Wu Jianqing and Ping Zha. "Treatment Strategies for Reducing Damages to Lungs In Patients with Coronavirus and Other Infections”. Available at SSRN 3533279 (2020).
  36. Ferrario Carlos M., et al. "Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2”. Circulation20 (2005): 2605-2610.
  37. Ni Wentao., et al. "Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19”. Critical Care 1 (2020): 1-10.
  38. Quiles José L., et al. "Do nutrients and other bioactive molecules from foods have anything to say in the treatment against COVID-19?" Environmental Research 191 (2020): 110053.
  39. Cure Erkan and Medine Cumhur Cure. "Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be harmful in patients with diabetes during COVID-19 pandemic”. Diabetes and Metabolic Syndrome: Clinical Research and Reviews (2020).
  40. Yang Penghui., et al. "Angiotensin-converting enzyme 2 (ACE2) mediates influenza H7N9 virus-induced acute lung injury”. Scientific Reports 4 (2014): 7027.
  41. Hochberg Ze'ev and Yossef Weisman. "Calcitriol-resistant rickets due to vitamin D receptor defects”. Trends in Endocrinology and Metabolism6 (1995): 216-220.
  42. Zinser Glendon M., et al. "Vitamin D receptor (VDR) ablation alters carcinogen-induced tumorigenesis in mammary gland, epidermis and lymphoid tissues”. The Journal of Steroid Biochemistry and Molecular Biology 1-2 (2005): 153-164.
  43. Li Yan Chun., et al. "1, 25-Dihydroxyvitamin D 3 is a negative endocrine regulator of the renin-angiotensin system”. The Journal of Clinical Investigation 2 (2002): 229-238.
  44. Jakovac Hrvoje. "COVID-19 and vitamin D-Is there a link and an opportunity for intervention?" American Journal of Physiology-Endocrinology and Metabolism 5 (2020): E589-E589.
  45. Teymoori‐Rad Majid and Sayed Mahdi Marashi. "Vitamin D and Covid‐19: From potential therapeutic effects to unanswered questions”. Reviews in Medical Virology (2020): e2159.
  46. Rhodes Jonathan M., et al. "Perspective: Vitamin D deficiency and COVID‐19 severity–plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis”. Journal of Internal Medicine (2020).
  47. Vyas Navya., et al. "Vitamin D in prevention and treatment of COVID-19: current perspective and future prospects”. Journal of the American College of Nutrition (2020): 1-14.
  48. Muthusamy Karthikeyan and Selvaraman Nagamani. "Vitamin D receptor (VDR) non-synonymous single nucleotide polymorphisms (nsSNPs) affect the calcitriol drug response-A theoretical insight”. Journal of Molecular Graphics and Modelling 81 (2018): 14-24.
  49. Liu Jun., et al. "Losartan inhibits conventional dendritic cell maturation and Th1 and Th17 polarization responses: Νovel mechanisms of preventive effects on lipopolysaccharide-induced acute lung injury”. International Journal of Molecular Medicine2 (2012): 269-276.
  50. Kolb Andreas F and Linda Petrie. "Folate deficiency enhances the inflammatory response of macrophages”. Molecular Immunology2 (2013): 164-172.
Citation: Karthikeyan Muthusamy., et al. “Association of Vitamin-D and VDR with ACE2 Modulates the Severity in COVID-19”.EC Orthopaedics 12.2 (2021): 87-92.

PubMed Indexed Article


EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005


EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777


EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347


EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478


EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253


EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033


EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992


EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505


EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793


EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211


EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047


EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560


EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318


EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819


EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840


EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344


EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476


EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658


EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489


EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278


EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108


EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571


EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333


EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883


EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001


EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937


EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723


EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726


EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603


EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646


EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616


EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290


EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226


EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812


EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268


News and Events


April Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the April issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for upcoming Issue

Ecronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before April 26, 2021.

Certificate of Publication

Ecronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

Ecronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.

Immediate Assistance

The prime motto of this team is to clarify all the queries without any delay or hesitation to avoid the inconvenience. For immediate assistance on your queries please don't hesitate to drop an email to editor@ecronicon.uk