Phylogenic analysis of coronavirus genome and molecular studies on potential anti-COVID-19 agents from selected FDA-approved drugs.
J Biomol Struct Dyn
; 40(17): 7726-7743, 2022 10.
Article
in English
| MEDLINE | ID: covidwho-1145107
ABSTRACT
The emergence of 2019 novel Coronavirus (COVID-19 or 2019-nCoV) has caused significant global morbidity and mortality with no consensus specific treatment. We tested the hypothesis that FDA-approved antiretrovirals, antibiotics, and antimalarials will effectively inhibit COVID-19 two major drug targets, coronavirus nucleocapsid protein (NP) and hemagglutinin-esterase (HE). To test this hypothesis, we carried out a phylogenic analysis of coronavirus genome to understand the origins of NP and HE, and also modeled the proteins before molecular docking, druglikeness, toxicity assessment, molecular dynamics simulation (MDS) and ligand-based pharmacophore modeling of the selected FDA-approved drugs. Our models for NP and HE had over 95% identity with templates 5EPW and 3CL5 respectively in the PDB database, with majority of the amino acids occupying acceptable regions. The active sites of the proteins contained conserved residues that were involved in ligand binding. Lopinavir and ritonavir possessed greater binding affinities for NP and HE relative to remdesivir, while levofloxacin and hydroxychloroquine were the most notable among the other classes of drugs. The Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), Radius of gyration (Rg), and binding energy values obtained after 100 ns of MDS revealed good stability of these compounds in the binding sites of the proteins while important pharmacophore features were also identified. The study showed that COVID-19 likely originated from bat, owing to the over 90% genomic similarity observed, and that lopinavir, levofloxacin, and hydroxychloroquine might serve as potential anti-COVID-19 lead molecules for additional optimization and drug development for the treatment of COVID-19.Communicated by Ramaswamy H. Sarma.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
COVID-19 Drug Treatment
/
Antimalarials
Limits:
Humans
Language:
English
Journal:
J Biomol Struct Dyn
Year:
2022
Document Type:
Article
Affiliation country:
07391102.2021.1902392
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