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Novel adenosine derivatives against SARS-CoV-2 RNA-dependent RNA polymerase: an in silico perspective.
Sonousi, Amr; Mahran, Hanan A; Ibrahim, Ibrahim M; Ibrahim, Mohamed N; Elfiky, Abdo A; Elshemey, Wael M.
  • Sonousi A; Pharmaceutical Organic Department, Faculty of Pharmacy, Cairo University, Giza, Egypt.
  • Mahran HA; University of Hertfordshire Hosted By Global Academic Foundation, New Administrative Capital, Cairo, Egypt.
  • Ibrahim IM; Biophysics Department, Faculty of Sciences, Cairo University, Giza, Egypt.
  • Ibrahim MN; Biophysics Department, Faculty of Sciences, Cairo University, Giza, Egypt.
  • Elfiky AA; Clinical Laboratories Department, College of Applied Medical Sciences, Jouf University, Sakakah, Kingdom of Saudi Arabia.
  • Elshemey WM; Microbiology Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
Pharmacol Rep ; 73(6): 1754-1764, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1283833
ABSTRACT

BACKGROUND:

SARS-CoV-2 is a newly emerged human coronavirus that severely affected human health and the economy. The viral RNA-dependent RNA polymerase (RdRp) is a crucial protein target to stop virus replication. The adenosine derivative, remdesivir, was authorized for emergency use 10 months ago by the United States FDA against COVID-19 despite its doubtful efficacy against SARS-CoV-2.

METHODS:

A dozen modifications based on remdesivir are tested against SARS-CoV-2 RdRp using combined molecular docking and dynamics simulation in this work.

RESULTS:

The results reveal a better binding affinity of 11 modifications compared to remdesivir. Compounds 8, 9, 10, and 11 show the best binding affinities against SARS-CoV-2 RdRp conformations gathered during 100 ns of the Molecular Dynamics Simulation (MDS) run (- 8.13 ± 0.45 kcal/mol, - 8.09 ± 0.67 kcal/mol, - 8.09 ± 0.64 kcal/mol, and - 8.07 ± 0.73 kcal/mol, respectively).

CONCLUSIONS:

The present study suggests these four compounds as potential SARS-CoV-2 RdRp inhibitors, which need to be validated experimentally.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Drug Design / Adenosine / Adenosine Monophosphate / Alanine / Coronavirus RNA-Dependent RNA Polymerase Type of study: Prognostic study Limits: Humans Language: English Journal: Pharmacol Rep Journal subject: Pharmacology Year: 2021 Document Type: Article Affiliation country: S43440-021-00300-9

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Drug Design / Adenosine / Adenosine Monophosphate / Alanine / Coronavirus RNA-Dependent RNA Polymerase Type of study: Prognostic study Limits: Humans Language: English Journal: Pharmacol Rep Journal subject: Pharmacology Year: 2021 Document Type: Article Affiliation country: S43440-021-00300-9