Natural Compounds From Djiboutian Medicinal Plants as Inhibitors of Covid-19 by in Silico Investigations

Abstract

Objective: The new coronavirus type SARS-Cov 2 (severe acute respiratory syndrome), which appeared in autumn 2019 in China, became a global pandemic in a few months. In this work, we looked for the potential anti SARS-Cov 2 of the compounds isolated from three Djiboutian medicinal plants, namely Acacia seyal, Cymbopogon commutatus, and Indigofera caerulea.
 Methods: We carried out a molecular docking with nine biomolecules, β-Sitosterol, Quercetin, Catechin, Lupeol, Rutin, Kaempferol, Gallic acid, Piperitone and Limonene on three target sites which are SARS-CoV-2 main protease (Mp), SARS-CoV-2 receptor-binding domain (RBD) and human furin protease. These targets are chosen because of their role in the process of penetration of the virus into human cells and its multiplication. Moreover, the predictions of pharmacokinetic parameters as well as toxicological properties have been determined using an online bioinformatics tool named SwissADME and AdmetSAR respectively.
 Results: The phenolic compounds have a very good affinity on these three target sites with binding energies of up to-9.098 kcal/mol for rutin on SARS-CoV-2 Mp, much better than the two reference drugs hydroxychloroquine (-5.816 kcal/mol) and remdesivir (-7.194 kcal/mol). Except for β-Sitosterol, the tested biomolecules have weak toxicity.
 Conclusion: These natural compounds can be used against covid 19 pending In vitro and In vivo evaluations.

Biomedical Effects of the Phytonutrients Turmeric, Garlic, Cinnamon, Graviola, and Oregano: A Comprehensive Review

“…Results showed a 74% HPV clearance in treated patients compared to the 25% clearance for the placebo group [206]. Furthermore, recent in silico studies suggest that rutin, a phytonutrient abundant in graviola, could act as strong ligands and inhibit the function of proteins of the SARS-CoV and SARS-CoV-2 virus, thus suggesting potential therapeutic benefits against the COVID-19 infection [207,208].…”

A Comprehensive Update of Various Attempts by Medicinal Chemists to Combat COVID-19 through Natural Products

“…were studied, out of which rutin 29, catechin 41, and kaempferol 23 exhibited lower binding energy values than the reference drug, hydroxychloroquine (−4.828 kcal/mol) against the SARS-CoV-2 receptor binding domain [69]. Amentoflavone 42 was found to be the best active compound against the spike proteins compared to the reference drug hydroxychloroquine, with a binding free energy of −6.4 kcal/mol.…”

“…Djiboutian medicinal plants and some natural products have potential as inhibitors of SARS-CoV-2’s M pro . Nine molecules have been studied, out of which rutin 29, catechin 41, and kaempferol 23 showed the best binding affinities with the M pro compared to the reference drug, remdesivir (−7.194 kcal/mol) [ 69 ], whereas amentoflavone 42 was found to be the best active compound compared to the reference drug hydroxychloroquine with a binding free energy value of −6.3 kcal/mol. Lipinski’s rule of five also showed its drug-like properties.…”

“…Hesperidin 51 and nabiximols 179 ( Figure 11 ) performed inhibitory activity against spike proteins with binding free energy values compared to the standard drugs nelfinavir, hydroxychloroquine sulphate, and chloroquine [ 86 ]. Nine molecules from Djiboutian medicinal plants were studied, out of which rutin 29 , catechin 41 , and kaempferol 23 exhibited lower binding energy values than the reference drug, hydroxychloroquine (−4.828 kcal/mol) against the SARS-CoV-2 receptor binding domain [ 69 ]. Amentoflavone 42 was found to be the best active compound against the spike proteins compared to the reference drug hydroxychloroquine, with a binding free energy of −6.4 kcal/mol.…”

“…For example, amentoflavone 42, one of the most abundant plant flavonoids, is proposed as a lead candidate with its ability to inhibit spike glycoproteins, viral proteases (M pro and PL pro ), and RdRp activities of the virus, as well as to inhibit the ACE2 activity of the host cell [ 61 , 78 , 79 ]. Rutin 29 , which is a flavonoid glycoside, showed inhibitory effects on the main protease, PL pro , RBD-ACE2 complex, nucleocapsid, and endoribonuclease [ 68 , 69 , 85 , 118 ]. Apart from this, many other flavonoids (myricetin 33 [ 54 , 55 ], baicalein 16 [ 31 , 32 ], kaempferol 23 [ 54 , 57 ], quercetin 40 [ 54 , 60 ], and catechins 41 [ 54 , 60 , 69 ]) have been found to display encouraging in silico outcomes against the COVID-19 disease.…”