Phytochemicals of Rhus spp. as Potential Inhibitors of the SARS-CoV-2 Main Protease: Molecular Docking and Drug-Likeness Study

Abstract

Background. The outbreak of coronavirus disease 2019 (COVID-19) induced by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in China and spread to cover the entire world with an ongoing pandemic. The magnitude of the situation and the fast spread of the new and deadly virus, as well as the lack of specific treatment, led to a focus on research to discover new therapeutic agents. Aim. In this study, we explore the potential inhibitory effects of some active polyphenolic constituents of Rhus spp. (sumac) against the SARS-CoV-2 main protease enzyme (Mpro; 6LU7). Methods. 26 active polyphenolic compounds of Rhus spp. were studied for their antiviral activity by molecular docking, drug likeness, and synthetic accessibility score (SAS) as inhibitors against the SARS-CoV-2 Mpro. Results. The results show that all tested compounds of sumac provided good interaction with the main active site of SARS-CoV-2 Mpro, with better, lower molecular docking energy (kcal/mol) compared to the well-known drugs chloroquine and favipiravir (Avigan). Only six active polyphenolic compounds of Rhus spp. (sumac), methyl 3,4,5-trihydroxybenzoate, (Z)-1-(2,4-dihydroxyphenyl)-3-(3,4-dihydroxyphenyl)-2-hydroxyprop-2-en-1-one, (Z)-2-(3,4-dihydroxybenzylidene)-6-hydroxybenzofuran-3(2H)-one, 3,5,7-trihydroxy-2-(4-hydroxyphenyl)chroman-4-one, 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-methoxy-4H-chroman-4-one, and 3,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one, were proposed by drug likeness, solubility in water, and SAS analysis as potential inhibitors of Mpro that may be used for the treatment of COVID-19. Conclusion. Six phenolic compounds of Rhus spp. are proposed for synthesis as potential inhibitors against Mpro and have potential for the treatment of COVID-19. These results encourage further in vitro and in vivo investigations of the proposed ligands and research on the preventive use of Rhus spp. against SARS-CoV-2.

Molecular docking studies of phytochemicals from Terminalia chebula for identification of potential multi-target inhibitors of SARS-CoV-2 proteins

“…studied the antiviral activity of 26 active polyphenolic compounds of Rhus spp . against SARS-CoV-2 main protease enzyme (M pro ; 6LU7) using molecular docking approach and identified six polyphenolic compounds as potential inhibitors based on drug likeness, solubility in water, and synthetic accessibility score (SAS) analysis ( Sherif, Gabr, Hosny, Alghadir, & Alansari, 2021 ). These polyphenols mainly interact through H-bonding, whereas, in our study, 1,3,6-Trigalloyl glucose, Beta-Sitosterol and Daucosterol interact primarily through hydrophobic residues along with H-bonding.…”

Phenolic compounds versus SARS-CoV-2: An update on the main findings against COVID-19

“…Specific areas of proteins are also investigated such as the protease domain (PD) of ACE2, the RBD (which binds to PD) of S protein ( Albohy et al, 2020 ), S1 (contains the RBD) and S2 (responsible for membrane fusion subsequent to the role of S1) subunit protein ( Harisna et al, 2021 ; Verma et al, 2020 ), and the protease enzyme 6LU7, which is the crystal structure of the 3CLpro ( Sherif et al, 2021 ). Arokiyaraj et al (2020) determined that kaempferol, kaempferol 7-o-rhamnoside, quercetin, kaempferitrin, geraniin, corilagin, protocatechuic acid, gallic acid and ellagic acid are compounds with the potential to inhibit the RBD activity of S protein of the SARS-CoV-2.…”

“… ACE2: (K353, D30, D38, E35, E37 and N33) a . Sherif et al (2021) Rhus spp . Methyl 3,4,5-trihydroxybenzoate Protease enzyme 6LU7 −81.82 (His164, Leu141¸ Cys145, Ser144 and Phe140) a .…”

A Global Picture: Therapeutic Perspectives for COVID-19

“…It has been reported that several natural compounds and their derivatives were effective against SARS-CoV-2 infection ( Supplementary Table 5 [ 147 , 148 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 ]) [ 160–163 ]. It has been documented that a number of herbal extracts belonging to the Polygonaceae family inhibit the interaction of viral S protein with host ACE2 [ 164 ], and one such example is emodin [ 165 ].…”