Experimental and theoretical study of novel amino‐functionalized P(V) coordination compounds suggested as inhibitor of M^Proof SARS‐COV‐2 by molecular docking study

Abstract

Amino-functionalized P(V) derivatives providing both N-and O-donor modes have attracted interest owing to their potential to form interesting coordination assemblies with applications such as biological drugs. Novel coordination modes of two-and four-dentate tris (pyridin-2-yl)phosphoric triamide OP [NH-2 Py] 3 as ([Co (II) .DMF, 2) have been synthesized and structurally studied. The metal center environment is distorted octahedral for 1 and distorted square pyramidal for 2. The crystal structure of a new complex of Cu (II) with a Cu[N] 4 [Cl] 2 environment ([Cu (II) Cl 2 (Pyrazole) 4 ], 3) is also investigated. An evaluation of the inhibitory effect against the coronavirus (Main Protease [M Pro ] of SARS-CoV-2) was carried out by a molecular docking study and illustrates that these compounds have a good interaction tendency with CoV-2, where 1 has the best binding affinity with the biological target comparable with other SARS-CoV-2 drugs. Moreover, theoretical QTAIM and natural bond orbital (NBO) calculations are used to evaluate the metal-oxygen/-nitrogen bonds suggesting that they are mainly electrostatic in nature with a slight covalent contribution. A molecular packing analysis using Hirshfeld surface (HS) analysis shows that N-H … O (in 1 and 2) and N-H … Cl (in 3) hydrogen bonds are the dominant interactions that contribute to the crystal packing cohesion. The semi-empirical PIXEL method indicates that the electrostatic and repulsion energy components in the structures of 1 and 2 and the dispersion and electrostatic components in that of 3 are the major contributors to the total lattice energy.

Structural, Hirshfeld surface and molecular docking studies of a new organotin(IV)-phosphoric triamide complex and an amidophosphoric acid ester proposed as possible SARS-CoV-2 and Monkeypox inhibitors

“…Such interactions by helping the phosphoryl group are not possible for the complex 1 , where the P═O group has been coordinated to the tin metal center as Sn⋯O═P. Furthermore, recently we have carried out the molecular docking study on the different families of phosphoramides (phosphoric triamides [ 17 , 28 ], amidophosphoric acid esters [ 27 ] and some of phosphoric triamide Co 2+ and Cu 2+ complexes [ 19 ]) to evaluate their inhibitory activity against M Pro of SARS-CoV-2. The results of these studies show the negative binding energies in the range −4.7 to −6.9 kcal/mol for the ligand–protein interactions suggested as anti-coronavirus.…”

“…Antibacterial and antimicrobial properties also have been found for some of phosphoramidate derivatives [ [13] , [14] , [15] , [16] ]. Moreover, some of these compounds are found to be the significant promising candidates to inhibit coronavirus [ [17] , [18] , [19] ]: some of the current not-optimal anti-coronavirus drugs, Remdesivir and Sofosbuvir, belong to the phosphoramides family [ 20 , 21 ]. However, there are no reports of the inhibitory potential of phosphoramide compounds on Monkeypox.…”

Structural and Molecular Packing study of Three New Amidophosphoric Acid Esters and Assessment of Their Inhibiting Activity Against SARS‐CoV‐2 by Molecular Docking

“…R F improved in all cases slightly. The final HARed structures were used for the molecular docking studies as it is believed that these give more accurate binding energies than the structures refined with spherical form factors [15] . The molecular graphics were drawn by using the programs PLATON [41] and Mercury [42] …”

“…Clinical trials of new anti‐coronavirus drugs request a long time and equipment; therefore computer‐aided drug discovery such as molecular docking simulation which tests the binding interactions between the target protein of virus and the tested drug compound are being used to evaluate the activity of a drug and to accelerate the choice of potential drugs for clinical trials [10,11] . Some suitable antiviral drugs based on phosphoramides and phosphonates such as Tenofovir, Sofosbuvir and Remdesivir have been proposed as anti‐coronavirus agent [12–15] . Moreover, some phosphates‐based compounds were suggested as possible inhibitors against SARS‐CoV‐2 [16] .…”

“…[ 10 , 11 ] Some suitable antiviral drugs based on phosphoramides and phosphonates such as Tenofovir, Sofosbuvir and Remdesivir have been proposed as anti‐coronavirus agent. [ 12 , 13 , 14 , 15 ] Moreover, some phosphates‐based compounds were suggested as possible inhibitors against SARS‐CoV‐2. [16] There are, however, no reports of amidophosphoric acid esters as a sub‐class of phosphoramides to evalute their inhibitory effect on coronavirus.…”