Binding mechanism and structural insights into the identified protein target of COVID-19 and importin-α with in-vitro effective drug ivermectin (India 2020-10-28) Molecular study
Would someone please synthesize the molecular studies into a consensus finding?
Abstract
While an FDA approved drug Ivermectin was reported to dramatically reduce the cell line of SARS-CoV-2 by ∼5000 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.
[-] TrumpLyftAlles | 1 points | Nov 04 2020 04:04:00
Would someone please synthesize the molecular studies into a consensus finding?
Abstract
While an FDA approved drug Ivermectin was reported to dramatically reduce the cell line of SARS-CoV-2 by ∼5000 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.
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[-] Haitchpeasauce | 1 points | Nov 04 2020 23:22:09
This is the same study that I posted a few days back but hosted on NIH.
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