In silico identification of SARS-CoV-2 cell entry inhibitors from selected natural antivirals.

Şimşek Y., Baran S. S., Aslım B.

Journal of molecular graphics & modelling, cilt.109, ss.108038, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 109
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.jmgm.2021.108038
  • Dergi Adı: Journal of molecular graphics & modelling
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Applied Science & Technology Source, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, Chimica, Compendex, Computer & Applied Sciences, EMBASE, INSPEC, MEDLINE
  • Sayfa Sayıları: ss.108038
  • Anahtar Kelimeler: SARS-CoV-2, Antivirals, Spike protein, Neuropilin, ACE2, Molecular docking, Molecular dynamics simulation, MOLECULAR-DYNAMICS, ACCURATE DOCKING, SARS, CORONAVIRUS, PROTEIN, RIBAVIRIN, GLIDE, LOPINAVIR/RITONAVIR, PREDICTION, QUERCETIN
  • Gazi Üniversitesi Adresli: Evet

Özet

The aim of this study is to identify potential drug-like molecules against SARS-CoV-2 virus among the natural antiviral compounds published in the Encyclopedia of Traditional Chinese Medicine. To test inhibition capability of these compounds first, we docked them with Spike protein, angiotensin-converting enzyme 2 (ACE2) (PDB ID: 6M0J) and neuropilin 1 (NRP1) (PDB ID: 7JJC) receptors, and found significant docking scores with extra precision up to -11 kcal/mol. Then, their stability in the binding pockets were further evaluated with molecular dynamics simulation. Eight natural antiviral compounds were identified as potential inhibitors against SARSCoV-2 cell entry after 200 ns molecular dynamics simulations. We found CMP-3, CMP-4, CMP-5, CMP-6 and CMP-8 are strong binders for the spike protein, CMP-1, CMP-2, CMP-4, CMP-5 and CMP-7 are strong binders for the neuropilin receptor, and CMP-5 is a strong binder for the ACE2. Quercetin derivatives (CMP-4, CMP-5, CMP-6 and CMP-7) were found highly stable in the active domain of NRP1, ACE2 and Spike protein. Especially, CMP-5 showed an inhibitory activity for all targets. These natural antivirals may be potential drug candidates for the prevention of SARS-CoV-2 infection.