Ascorbic Acid as an Inhibitor for SARS-CoV-2 Virus Reproduction: A Theoretical Approach

  • Mohammed Abed Jawad Al-Nisour University College, Iraq.
  • Abed J Kadhim Al-Nisour University College, Iraq.
Keywords: COVID-19, Vitamin C, DFT, Docking, TED


In the present study, ascorbic acid’s or Vitamin C’s influence (VC) in inhibition of SARS-CoV-2 virus reproduction was investigated. Gaussian 09 with a basis set of 6-311G (d, p), MGL tools, DSV, and LigPlus software were used. According to the Total Electron Density (TED) and Millikan charges, the active sites for adsorption were determined. Further, the docking study had clearly revealed the role of VC in inhibition of the virus reproduction in accordance with binding energy (Eb) and ligand efficiency (LE). The vitamin’s interaction with the virus’s spikes may limit its replication or provide the immune system sufficient time to recognize the infection, which enhances the possibility of producing appropriate antibodies.

How to cite this article:
Jawad MA, Kadhim AJ. Ascorbic Acid as an Inhibitor for SARS-CoV-2 Virus Reproduction: A Theoretical Approach. J Commun Dis. 2021;53(3): 181-185.



Food and Nutrition Board. Dietary Reference Intakesfor Vitamin C, Vitamin E, Selenium, and Carotenoids.

Washington, DC: National Academy Press, 2000.

Pauling L. The significance of the evidence about ascorbic acid and the common cold. Proc Natl Acad

Sci U S A. 1971;68:2678-81. [PubMed] [Google Scholar]

While LA, Freeman CY, Forrester BD, Chappell WA. In vitro effect of ascorbic acid on infectivity of herpesviruses and paramyxoviruses. J Clin Microbiol. 1986 Oct;24(4):527-31. [PubMed] [Google Scholar]

Klein M. The mechanism of the virucidal action of ascorbic acid. Science. 1945 Jun;101(2632):587-9.

[PubMed] [Google Scholar]

Marik PE. Hydrocortisone, ascorbic acid and thiamine (HAT therapy) for the treatment of sepsis. Focus

on ascorbic acid. Nutrients. 2018 Nov;10(11):1762. [PubMed] [Google Scholar]

Uesato S, Kitagawa Y, Kaijima T, Tokuda H, Okuda M, Mou XY, Mukainaka T, Nishino H. Inhibitory effects of

-O-acylated L-ascorbic acids possessing a straight- or branched-acyl chain on epstein-barr virus activation.

Cancer Lett. 2001 May;166(2):143-6. [PubMed] [Google Scholar]

Cinatl J, Cinatl J, Weber B, Rabenau H, Gümbel HO, Chenot JF, Scholz M, Encke A, Doerr HW. In vitro

inhibition of human cytomegalovirus replication in human foreskin fibroblasts and endothelial cells

by ascorbic acid 2-phosphate. Antiviral Res. 1995 Aug;27(4):405-18. [PubMed] [Google Scholar]

Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017 Nov;9(11):1211. [PubMed] [Google


Leibovitz B, Siegel BV. Ascorbic acid and the immune response. Adv Exp Med Biol. 1981;135:1-25. [Google


Dey S, Bishayi B. Killing of S. aureus in murine peritoneal macrophages by ascorbic acid along with antibiotics

chloramphenicol or ofloxacin: correlation with inflammation. Microb Pathog. 2018 Feb;115:239-50.

[PubMed] [Google Scholar]

Sanders J, Monogue M, Jodlowski T, Cutrell J. Pharmacologic treatments for coronavirus disease

(COVID-19). JAMA. 2020 May;323(18):1824-36. [PubMed] [Google Scholar]

Bilbul M, Paparone P, Kim A, Mutalik S, Ernst C. Psychopharmacology of COVID-19. Psychosomatics.

Psychosomatics. 2020 Sep-Oct;61(5):411-27. [PubMed] [Google Scholar]

Carr A, Rosengrave P, Bayer S, Chambers S, Mehrtens J, Shaw G. Hypovitaminosis C and vitamin C deficiency

in critically ill patients despite recommended enteral and parenteral intakes. Crit Care. 2017 Dec;21(1):300.

[PubMed] [Google Scholar]

Earar K, Arbune M, Dorobat C, Rusu-Negraia M, Stefanescu V, Indrei L, Schipor O, Harabor VR, HaraborA, Bratu AM. Biochemical effects and therapeutic application of vitamin C (C6H8O6) on COVID-19

infection. Rev Chim. 2020;71(5):473-8. [Google Scholar]

Bauer S, Kapoor A, Rath M, Thomas S. What is the role of supplementation with ascorbic acid, zinc, vitamin

D, or N-acetylcysteine for prevention or treatment of COVID-19? Cleveland Clin J Med. 2020 Jun 8. [PubMed]

[Google Scholar]

Wang L, Wang Y, Ye D, Liu Q. Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence. Int J Antimicrob Agents. 2020 Jun;55(6):105948. [PubMed] [Google Scholar]

Wu J. Tackle the free radicals damage in COVID-19. Nitric Oxide. 2020 Sep;102:39-41. [PubMed] [Google Scholar]

Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z.

Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan,

China. JAMA. 2020 Mar;323(11):1061-9. [PubMed] [Google Scholar]

Kakodkar P, Kaka N, Baig M. A comprehensive literature review on the clinical presentation, and management

of the pandemic coronavirus disease 2019 (COVID-19). Cureus. 2020 Apr;12(4):e7560. [PubMed] [Google


Colunga Biancatelli R, Berrill M, Marik P. The antiviral properties of vitamin C. Expert Rev Anti Infect Ther.

Feb;18(2):99-101. [PubMed] [Google Scholar]

Gao Y, Lu B, Zhai J, Liu Y, Qi H, Yao Y, Chai Y-F, Shou S-T. The parenteral vitamin C improves sepsis and sepsisinduced multiple organ dysfunction syndrome via preventing cellular immunosuppression. Mediators

Inflamm. 2017;2017:1-12. [PubMed] [Google Scholar]

Boretti A, Banik B. Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome. PharmaNutrition. 2020 Jun;12:100190. [PubMed] [Google Scholar]

Adiloğlu SI, Yu C, Chen R, Li JJ, Li JJ, Drahansky M, Paridah M, Moradbak A, Mohamed A, Owolabi, FolaLi

H Abdulwahab Taiwo, Asniza M, Abdul Khalid SH, Sharma T, Dohare N, Kumari M, Singh UK, Khan AB,

Borse MS, Patel R, Paez A, Howe A, Goldschmidt D, Corporation C, Coates J, Reading F. We are IntechOpen,

the world’s leading publisher of open access books built by scientists, for scientists TOP 1%. Intech. 2012;i:13.

Yu JQ, Geng YL, Wang DJ, Zhao HW, Guo L, Wang X. Terpenes from the gum resin of Boswellia carterii

and their NO inhibitory activies. Phytochem. Lett. 2018;28:59-63. [Google Scholar]

Sayin K, Kariper SE, Taştan M, Sayin TA, Karakaş D. Investigations of structural, spectral, electronic and

biological properties of N-heterocyclic carbene Ag(I) and Pd(II) complexes. J. Mol. Struct. 2019;1176:478-87.

[Google Scholar]

Zimmermann-klemd AM, Reinhardt JK, Nilsu T, Morath A, Falanga CM, Schamel WW, Huber R, Hamburger

M, Gründemann C. Boswellia carteri extract and 3- O -acetyl-alpha-boswellic acid suppress T cell function.

Fitoterapia. 2020 Oct;146:104694. [PubMed] [Google Scholar]

Becke AD. Density-functional thermochemistry. III. The role of exact exchange. J. Chem. Phys. 1993;98:5648-52.

Lee C, Yang W, Parr RG. Development of the Colle-Salvetti correlation-energy formula into a functional of

the electron density. Phys Rev B Condens Matter. 1988 Jan;37(2):785-9. [PubMed] [Google Scholar]

Li H, Leung KS, Ballester PJ, Wong MH. istar: A web platform for large-scale protein-ligand docking. PLoS

One. 2014 Jan;9(1):e85678. [PubMed] [Google Scholar]

Hussein EA, Shaheed IM, Hatam RS, Kadhim MM, Al-kadhum DT. Adsorption, thermodynamic and DFT

studies of removal RS dye on the Iraq clay from aqueous solutions. Sys Rev Pharm. 2020;11(3):495-502. [Google


Li H, Leung KS, Ballester PJ, Wong MH. istar: A web platform for large-scale protein-ligand docking. PLoS

One. 2014 Jan;9(1):e85678. [PubMed] [Google Scholar]

Mustafa MK, Abbas WS, Ameerah MZ, Wesam RK. Inhibition of SARS-CoV-2 reproduction using

Boswellia carterii: A theoretical study. J. Mol. Liq. 2021 Sep;337:116440. [Google Scholar]

Salman AW, Haque RA, Kadhim MM, Malan FP, Ramasami P. Novel triazine-functionalized tetra-imidazolium

hexafluorophosphate salt: Synthesis, crystal structure and DFT study. J. Mol. Struct. 2019;1198:126902.

[Google Scholar]

Radhi AH, Du EAB, Khazaal FA, Abbas ZM, Aljelawi OH, Hamadan HD, Almashhadani HA, Kadhim MM.

HOMO-LUMO Energies and geometrical structures effect on corrosion inhibition for organic compounds

predict by DFT and PM3 methods. NeuroQuantology. 2020;18(1):37-45. [Google Scholar]

Khazaal FA, Kadhim MM, Hussein HF, Abbas ZM, Hamzah MS, Khudhair IA, Almashhadani HA, Abed HH, Saieed HS. Electronic transfers and (NLO) properties predicted by AB initio methods with prove experimentally.

NeuroQuantology. 2020;18(1):46-52. [Google Scholar]

Abdul E, Fanfoon DY, Al-uqaily RAH, Salman AM, Kadhim MM, Salman AW, Abbas ZM.1-Isoquinolinyl phenyl

ketone as a corrosion inhibitor : A theoretical study. Mater Today Proc. 2021;42(5):2241-6. [Google Scholar]

Eva AY, Rana AA, Majid HA, Ivan HR, Mustafa MK. Electrochemical, morphological and theoretical studies

of an oxadiazole derivative as an anti-corrosive agent for kerosene reservoirs in Iraqi refineries. Chem. Pap.

;4:9883-92. [Google Scholar]