Inhibition of COVID-19 RNA-Dependent RNA Polymerase by Natural Bioactive Compounds: Molecular Docking Analysis

Abstract

Till now there is no approved treatment for COVID-19. Phenolic compounds are known to have antiviral activity against many viruses such as HCV and HIV, through their phenol rings interaction with viral proteins and/or RNA, or via its regulating MAP kinase signaling in host cell defense. The present study aimed to assess polyphenolic compounds (gallic acid, quercetin, caffeine, resveratrol, naringenin, benzoic acid, oleuropein and ellagic acid) as COVID-19 RNA-dependent RNA polymerase (PDB ID 6M71) inhibitors, using a molecular docking. Molecular docking of these polyphenols were performed using Autodock 4.0 and Chimera 1.8.1 programs. Drug likeness and polyphenols pharmacokinetic properties were calculated using SWISSADME prediction website (http://www.swissadme.ch/). Remdesivir and ribavirin were used as standard antiviral drugs for comparison. Docking analysis results, ranked by binding energy value (ΔG) of several tested ligands toward COVID-19 polymerase were; remdesivir > gallic acid > quercetin > caffeine > ribavirin > resveratrol > naringenin > benzoic acid > oleuropein > ellagic acid. The binding energies were -8.51, - 7.55, - 7.17, -6.10, - 6.01, - 5.79, - 5.69, - 5.54, - 4.94 and -4.59 kcal/mol, respectively. All tested polyphenols performed hydrogen bonds with one or two of the nucleotide triphosphate entry channel (NTP) amino acids in COVID-19 polymerase (ARG 555, ARG 555, LYS 545), except caffeine and oleuropein. Binding of polyphenols to NTP of COVID-19 polymerase may influence in the entry of the substrate and divalent cations into the central active site cavity, inhibiting the enzyme activity. It appears promising that, gallic acid and quercetin exhibited high binding affinity than ribavirin toward COVID-19 polymerase and expressed good drug likeness and pharmacokinetic properties. Therefore, gallic acid and quercetin may represent a potential treatment option for COVID-19. Further researches are urgently required to investigate the potential uses of these polyphenols in COVID-19 treatment. Additionally, resveratrol, naringenin, benzoic and ellagic acid seem to have the best potential to act as COVID-19 polymerase inhibitors.

Current Prevention of COVID-19: Natural Products and Herbal Medicine

“…The molecular structure of RdRp was revealed in May 2020 ( Gao Y. et al., 2020 ), providing a new strategy for discovering prophylactic candidates for SARS-CoV-2 inhibition. Abd El-Aziz et al ( El-Aziz Abd et al., 2020 ) investigated the potential of eight natural polyphenols (quercetin, naringenin, caffeine, oleuropein, ellagic acid, benzoic acid, resveratrol, and gallic acid polyphenols) as inhibitors of SARS-CoV-2 RdRp by molecular docking assay. The studied polyphenols formed hydrogen bonds with the nucleotide triphosphate (NTP) entry channel amino acids (ARG 555, ARG 555, LYS 545) in SARS-CoV-2 RdRp (except caffeine and oleuropein).…”

Fenolik Bileşik Oleuropein ve Hidroliz Ürünü 3-Hidroksitirozol'ün SARS-CoV-2'nin Bazı Yapısal ve Yapısal Olmayan Proteinlerine Karşı In Siliko Etkinliği

“…In a drug repurposing study performed with the Glide docking module, oleuropein exhibited -9.21 kcal mol -1 (in the absence of Mg 2+ ) and -6.07 kcal mol -1 (in the presence of Mg +2 ) docking scores against the RdRp enzyme (Kandeel et al, 2020). However, in another molecular docking study performed with Chimera 1.8.1, oleuropein showed a binding affinity of -4.59 kcal mol -1 to RdRp and interacted with the amino acids Asp445, Asp452, Tyr455 and Asn552 (Abd El- Aziz et al, 2020). This reported binding free energy value is considerably lower (rather weak) compared with the highly favorable binding affinity (-8.0 kcal mol -1 ) in our study.…”

Targeting Neurological Manifestations of Coronaviruses by Candidate Phytochemicals: A Mechanistic Approach

“…Also, Singh et al (2020) showed that theaflavin-3,3′-digallate, theaflavin-3′-gallate, theaflavin-3′- O -gallate, and theaflavin had the highest affinity for RdRp with -9.9, -9.6, -9.6, and -9.3 kcal/mol bonding energy, respectively. EGCG and hesperidin ( Singh et al, 2020 ), isolophirachalcone A ( Parvez et al, 2020 ), gallic acid and resveratrol ( Abd El-Aziz et al, 2020 ) are other polyphenols with anti-SARS-CoV-2 activities through the high binding affinity to RdRp.…”