Modeling studies on the role of vitamins B1 (thiamin), B3 (nicotinamide), B6 (pyridoxamine), and caffeine as potential leads for the drug design against COVID-19

Abstract

In response to the COVID-19 pandemic, and the lack of effective and safe antivirals against it, we adopted a new approach in which food supplements with vital antiviral characteristics, low toxicity, and fast excretion have been targeted. The structures and chemical properties of the food supplements were compared to the promising antivirals against SARS-COV-2. Our goal was to exploit the food supplements to mimic the topical antivirals' functions but circumventing their severe side effects, which has limited the necessary dosage needed to exhibit the desired antiviral activity. On this line, after a comparative structural analysis of the chemicals mentioned above, and investigation of their potential mechanisms of action, we selected caffeine and some compounds of the vitamin B family and further applied molecular modeling techniques to evaluate their interactions with the RDB domain of the Spike protein of SARS-CoV-2 (SC2Spike) and its corresponding binding site on human ACE-2 (HssACE2). Our results pointed to vitamins B1 and B6 in the neutral form as potential binders to the HssACE2 RDB binding pocket that might be able to impair the SARS-CoV-2 mechanism of cell invasion, qualifying as potential leads for experimental investigation against COVID-19.

Preparation of Vitamin-g-Lignin Nanohybrids with Excellent Biological Activity and Fluorescence Performance

“…The Schiff base portion with CN bonds was generated by the Schiff base reaction between lignin carbonyl with EDA and vitamin B 1 . According to the chemical structure, the reaction between the carboxyl and carbonyl active site of lignin and the amino group of EDA and vitamin B 1 can, to some extent, alter the original structure of lignin, introducing imine, quaternary ammonium ions, and amide structures that can reduce the absolute potential value (Figure ), which makes it easier for LEV to adhere to and interact with the negatively charged bacterial phospholipid membranes and cause bacterial lysis and death. ,− Meanwhile, H + dissociated from Ar–OH can penetrate the bacteria membranes, altering the internal physiological environment of bacteria and ultimately leading to bacteria death. At the same time, after hydrothermal modification, the presence of electron-donating groups such as nitromethyl and amide groups in LEV disrupts the balance of electron movement toward the benzene ring, and the H + on Ar–OH is more easily cleaved to form phenoxy radicals. , When in contact with bacteria, it will induce oxidative stress by changing the normal redox physiological process, affecting bacterial growth.…”

“…Vitamin B 1 is a derivative of pyrrolidone and is mainly synthesized by microorganisms and plants, which includes a pyrrole (thiophene, thiazole) and a pyridine ring in its structure. 30 VB 1 is positively charged and contains heteroatoms N and S, which can be doped with heteroatoms by the hydrothermal method to enhance the fluorescence performance and biological activity of nanoparticles. In this work, we first modified lignin nanoparticles using ethylenediamine and vitamin B 1 via the hydrothermal method.…”

Molecular modeling study of natural products as potential bioactive compounds against SARS-CoV-2

“…As in previous studies [ 22 , 23 ], the search space for molecular docking was defined to include all residues of the RBD of SC2Spike that interact with Hss ACE-2: Lys417, Gly446, Tyr449, Tyr453, Leu455, Phe456, Ala475, Phe486, Asn487, Tyr489, Gln493, Gly496, Gln498, Thr500, Asn501, Gly502, and Tyr505 [ 3 , 7 ]. The search space was a sphere with a radius of 23 Å and its center located at coordinates x = 215, y = 211, and z = 217.25.…”

“…The stability of temperature and pressure was maintained using the velocity-rescale thermostat and the Parrinello-Rahman pressure coupling method, respectively. Results of the MD simulations were analyzed through plots of RMSD, root mean square deviation fluctuation (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), and H-bonds, similar to works already reported in the literature [ 22 , 23 , 41 , 42 ]. Graphs and figures were generated using xmgrace 5.1.25 and Visual Molecular Dynamics 1.9.3 (VMD) [ 43 ].…”

Changing Health Lifestyles After the Pandemic

“…Vitamins A, D, C and B complex are the most studied and claimed to be the most effective in resistance to disease. However, detailed studies are still ongoing [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23].…”