Binding mechanism and structural insights into the identified protein target of COVID-19 and importin-α with in-vitro effective drug ivermectin.
J Biomol Struct Dyn
; 40(5): 2217-2226, 2022 Mar.
Article
in English
| MEDLINE | ID: covidwho-1214172
ABSTRACT
While an FDA approved drug Ivermectin was reported to dramatically reduce the cell line of SARS-CoV-2 by â¼5000 folds within 48 h, the precise mechanism of action and the COVID-19 molecular target involved in interaction with this in-vitro effective drug are unknown yet. Among 12 different COVID-19 targets along with Importin-α studied here, the RNA dependent RNA polymerase (RdRp) with RNA and Helicase NCB site show the strongest affinity to Ivermectin amounting -10.4 kcal/mol and -9.6 kcal/mol, respectively, followed by Importin-α with -9.0 kcal/mol. Molecular dynamics of corresponding protein-drug complexes reveals that the drug bound state of RdRp with RNA has better structural stability than the Helicase NCB site and Importin-α, with MM/PBSA free energy of -187.3 kJ/mol, almost twice that of Helicase (-94.6 kJ/mol) and even lower than that of Importin-α (-156.7 kJ/mol). The selectivity of Ivermectin to RdRp is triggered by a cooperative interaction of RNA-RdRp by ternary complex formation. Identification of the target and its interaction profile with Ivermectin can lead to more powerful drug designs for COVID-19 and experimental exploration.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pharmaceutical Preparations
/
COVID-19 Drug Treatment
Type of study:
Experimental Studies
Limits:
Humans
Language:
English
Journal:
J Biomol Struct Dyn
Year:
2022
Document Type:
Article
Affiliation country:
07391102.2020.1839564
Similar
MEDLINE
...
LILACS
LIS