Double chelation of Iron through dimer formation of favipiravir: Density functional theory analysis

Article type: Research Article

Authors: Ansari, Mohammad Javed^a | Jasim, Saade Abdalkareem^b | Abed, Azher M.^c | Altimari, Usama S.^d | Yasin, Ghulam^e | Suksatan, Wanich^f | Oudaha, Khulood H.^g | Kadhim, Mustafa M.^{h; i; j} | Jabbar, Abdullah Hasan^{k; *} | Mustafa, Yasser Fakri^l

Affiliations: [a] Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj, Saudi Arabia | [b] Medical Laboratory Techniques Department, Al-Maarif University College, Al-Anbar-Ramadi, Iraq | [c] Department of Air Conditioning and Refrigeration, Al-Mustaqbal University College, Babylon, Iraq | [d] Al-Nisour University College, Baghdad, Iraq | [e] Department of Botany, Bahauddin Zakariya University, Multan, Pakistan | [f] Faculty of Nursing, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand | [g] Pharmaceutical Chemistry Department, College of Pharmacy, Al-Ayen University, Thi-Qar, Iraq | [h] Department of Dentistry, Kut University College, Kut, Wasit, Iraq | [i] College of Technical Engineering, The Islamic University, Najaf, Iraq | [j] Department of Pharmacy, Osol Aldeen University College, Baghdad, Iraq | [k] Optical Department, College of Medical and Health Technology, Sawa University, Ministry of Higher Education and Scientific Research, Al-Muthanaa, Samawah, Iraq | [l] Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, Iraq

Correspondence: [*] Corresponding author: Abdullah Hasan Jabbar, Optical Department, College of Medical and Health Technology, Sawa University, Ministry of Higher Education and Scientific Research, Al-Muthanaa, Samawah, Iraq. E-mail: abdullah.hasan.j@sawa-un.edu.iq.

Abstract: This work was performed to examine an idea about full chelation of Iron (Fe) by well-known favipiravir (Fav) as a possible mechanism of action for medication of COVID-19 patients. To this aim, formations of Fe- mediated dimers of Fav were investigated by performing density functional theory (DFT) computations of electronic and structural features for singular and dimer models. The results indicated that the models of dimers were suitable for formation, in which two cis (D1) and trans (D2) models were obtained regarding the configurations of two Fav counterparts towards each other. Energy results indicated that formation of D1 was slightly more favorable than formation of D2. Molecular orbital features affirmed hypothesized interacting sites of Fav for Fe-mediated dimers formations, in which atomic charges and other molecular orbital related representations affirmed such achievements. Moreover, detection of such dimer formation was also possible by monitoring variations of molecular orbitals features. As a consequence, formations of Fe-mediated dimers of Fav could be achievable for possible removal of excess of Fe as a proposed mechanism of action for Fav in medication of COVID-19 patients.

Keywords: Favipiravir, iron chelation, dimerization, DFT, COVID-19

DOI: 10.3233/MGC-210182

Journal: Main Group Chemistry, vol. 21, no. 3, pp. 875-883, 2022