Targeting 3CLpro and SARS-CoV-2 RdRp by Amphimedon sp. Metabolites: A Computational Study

Nourhan Hisham Shady; Alaa M Hayallah; Mamdouh F A Mohamed; Mohammed M Ghoneim; Garri Chilingaryan; Mohammad M Al-Sanea; Mostafa A Fouad; Mohamed Salah Kamel; Usama Ramadan Abdelmohsen

doi:10.3390/molecules26123775

Targeting 3CLpro and SARS-CoV-2 RdRp by Amphimedon sp. Metabolites: A Computational Study

Molecules. 2021 Jun 21;26(12):3775. doi: 10.3390/molecules26123775.

Authors

Nourhan Hisham Shady¹, Alaa M Hayallah^{2

3}, Mamdouh F A Mohamed⁴, Mohammed M Ghoneim^{5

6}, Garri Chilingaryan^{7

8}, Mohammad M Al-Sanea⁹, Mostafa A Fouad¹⁰, Mohamed Salah Kamel^{1

10}, Usama Ramadan Abdelmohsen^{1

10}

Affiliations

¹ Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, Universities Zone, New Minia City 61111, Egypt.
² Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
³ Pharmaceutical Chemistry Department, Faculty of Pharmacy, Sphinx University, New Assiut 71515, Egypt.
⁴ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt.
⁵ Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Saudi Arabia.
⁶ Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Cairo 11371, Egypt.
⁷ Institute of Molecular Biology of NAS RA, Yerevan 0014, Armenia.
⁸ Institute of Biomedicine and Pharmacy, Russian-Armenian University, Yerevan 0051, Armenia.
⁹ Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Aljouf 72341, Saudi Arabia.
¹⁰ Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.

Abstract

Since December 2019, novel coronavirus disease 2019 (COVID-19) pandemic has caused tremendous economic loss and serious health problems worldwide. In this study, we investigated 14 natural compounds isolated from Amphimedon sp. via a molecular docking study, to examine their ability to act as anti-COVID-19 agents. Moreover, the pharmacokinetic properties of the most promising compounds were studied. The docking study showed that virtually screened compounds were effective against the new coronavirus via dual inhibition of SARS-CoV-2 RdRp and the 3CL main protease. In particular, nakinadine B (1), 20-hepacosenoic acid (11) and amphimedoside C (12) were the most promising compounds, as they demonstrated good interactions with the pockets of both enzymes. Based on the analysis of the molecular docking results, compounds 1 and 12 were selected for molecular dynamics simulation studies. Our results showed Amphimedon sp. to be a rich source for anti-COVID-19 metabolites.

Keywords: Amphimedon sp.; COVID-19; coronavirus; molecular docking; sponge.

MeSH terms

Amino Sugars / chemistry
Amino Sugars / pharmacology
Animals
Antiviral Agents / chemistry
Antiviral Agents / pharmacology
Binding Sites
Biological Products / chemistry*
Biological Products / isolation & purification
Biological Products / pharmacokinetics
Biological Products / pharmacology*
COVID-19 Drug Treatment
Computational Biology
Coronavirus 3C Proteases / antagonists & inhibitors
Coronavirus 3C Proteases / chemistry*
Coronavirus 3C Proteases / metabolism
Humans
Ligands
Models, Molecular
Molecular Docking Simulation
Molecular Dynamics Simulation
Porifera / chemistry*
Porifera / metabolism*
Protease Inhibitors / chemistry
Protease Inhibitors / pharmacology
Pyridines / chemistry
Pyridines / pharmacology
RNA-Dependent RNA Polymerase / antagonists & inhibitors
RNA-Dependent RNA Polymerase / chemistry*
RNA-Dependent RNA Polymerase / metabolism
SARS-CoV-2 / drug effects*
SARS-CoV-2 / enzymology
SARS-CoV-2 / metabolism

Substances

Amino Sugars
Antiviral Agents
Biological Products
Ligands
Protease Inhibitors
Pyridines
amphimedoside C
nakinadine B
RNA-Dependent RNA Polymerase
Coronavirus 3C Proteases