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Chemical constituents from coconut waste and their in silico evaluation as potential antiviral agents against SARS-CoV-2.


ABSTRACT: Eleven compounds were isolated from the ethyl acetate extract of Cocos nucifera L endocarp, jezonofol 1, scirpusin A 2, cassigarol G 3, maackin A 4, threoguiacyl glycerol-8'-vanillic acid ether 5, erythroguiacyl glycerol-8'-vanillic acid ether 6, apigenin-7-O-β-D-glucoside 7, piceatannol 8, p-hydroxy-benzoic acid 9, protocatechuic acid 10 and vanillic acid 11. Compounds 1-7 were isolated for the first time from the plant. The isolated compounds were virtually screened against four critical components of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), the main protease (Mpro), papain-like protease (PLpro), nonstructural protein 13 (nsp13) and RNA dependent RNA polymerase (RdRp). Stilbene dimers 1-4 showed remarkable binding affinities towards the investigated targets (binding energy <-7.6 kcal/mol). Compounds 1, 3 and 4 interacted with the catalytic dyad (Cys145-His41) at the active pocket of Mpro which is essential for achieving good inhibitory activity. Compounds 1-3 showed molecular interaction with the conserved ubiquitin-specific protease residues of PLpro, responsible for binding ability at different active sites of nsp13, which are crucial for decreasing the resistance caused by viral immune evasion. Compounds 2 and 3 showed the ability to bind at different active sites of nsp13, which is a key binding site for reducing antiviral resistance. Finally, compounds 1-3 showed the ability to bind with RdRp before and after RNA binding. Our findings suggested that the dimeric stilbene skeleton is a promising candidate for developing anti-COVID-19 drugs. Particularly, 1, 2 and 3, showed a promiscuity pattern binding to multiple targets of SARS-CoV-2 replication. Herein, 20 ns molecular dynamics (MD) simulations combined with molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations were performed to estimate the binding affinity of the most potent three compounds against the viral SARS-CoV-2 targets. MM-GBSA calculations unveiled the outshine potency of compound 1 towards PLpro with a binding energy of -60.7 kcal/mol. Structural and energetic analyses over 20 ns MD simulation displayed the high stability of compound 1 in complex with PLpro. The list of the compounds was considered herein forms a primer for clinical investigation in COVID-19 patients and directing for further antiviral examinations. Drug likeness properties of compounds 1-4 were evaluated.

SUBMITTER: Elsbaey M 

PROVIDER: S-EPMC8162769 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Chemical constituents from coconut waste and their <i>in silico</i> evaluation as potential antiviral agents against SARS-CoV-2.

Elsbaey Marwa M   Ibrahim Mahmoud A A MAA   Bar Fatma Abdel FA   Elgazar Abdullah A AA  

South African Journal of Botany. 20210528


Eleven compounds were isolated from the ethyl acetate extract of <i>Cocos nucifera</i> L endocarp, jezonofol <b>1</b>, scirpusin A <b>2</b>, cassigarol G <b>3</b>, maackin A <b>4</b>, threoguiacyl glycerol-8'-vanillic acid ether <b>5</b>, erythroguiacyl glycerol-8'-vanillic acid ether <b>6</b>, apigenin-7-<i>O</i>-<i>β</i>-D-glucoside <b>7</b>, piceatannol <b>8</b>, <i>p</i>-hydroxy-benzoic acid <b>9</b>, protocatechuic acid <b>10</b> and vanillic acid <b>11</b>. Compounds <b>1</b>-<b>7</b> were  ...[more]

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