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Covalent Inhibition in Drug Discovery: Filling the Void in Literature

[ Vol. 18 , Issue. 13 ]

Author(s):

Imane Bjij, Fisayo A. Olotu, Clement Agoni, Emmanuel Adeniji, Shama Khan, Ahmed El Rashedy, Driss Cherqaoui and Mahmoud E.S. Soliman*   Pages 1135 - 1145 ( 11 )

Abstract:


The serendipitous discovery of covalent inhibitors and their characteristic potency of inducing irreversible and complete inhibition in therapeutic targets have caused a paradigm shift from the use of non-covalent drugs in disease treatment. This has caused a significant evolution in the field of covalent targeting to understand their inhibitory mechanisms and facilitate the systemic design of novel covalent modifiers for ‘undruggable’ targets. Computational techniques have evolved over the years and have significantly contributed to the process of drug discovery by mirroring the pattern of biological occurrences thereby providing insights into the dynamics and conformational transitions associated with biomolecular interactions. Moreover, our previous contributions towards the systematic design of selective covalent modifiers have revealed the various setbacks associated with the use of these conventional techniques in the study of covalent systems, hence there is a need for distinct approaches. In this review, we highlight the modifications and development of computational techniques suitable for covalent systems, their lapses, shortcomings and recent advancements.

Keywords:

Covalent, Irreversible, Inhibition, Computational techniques, Molecular dynamics, Covalent docking, QM/MM.

Affiliation:

Molecular Biocomputation and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4000, Molecular Biocomputation and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4000, Molecular Biocomputation and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4000, Molecular Biocomputation and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4000, Molecular Biocomputation and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4000, Molecular Biocomputation and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4000, Universite Cadi Ayyad, Faculte des Sciences Semlalia, Departement de Chimie, Av. My Abdellah, BP2390 Marrakech, Molecular Biocomputation and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4000

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