Molecular Dynamics Simulation of SARS-CoV-2 E Ion Channel: The Study of Lone Protein and its Conformational Changes in Complex with Potential Cage Inhibitors.

Background: The coronavirus E ion channel has previously been studied as a potential target for antiviral therapy, with several compounds found to bind to the channel. However, these compounds have low activity, searching for effective E ion channel inhibitors of great importance.

Objective: This study aimed to develop a computational approach for designing ligands for the coronaviral E ion channel and identify potential inhibitors based on this approach.

Towards a qualitative understanding of the carbonyl reactivity of α-substituted ethyl 5-oxohomoadamantyl-4-carboxylates.

Substituted ethyl 5-oxohomoadamantane-4-carboxylates were subjected to reactions with several nucleophiles to establish some aspects of the carbonyl reactivity. However, only one example of the desired Claisen retro-reaction was observed as 3,7-disubstituted bicyclo[3.3.

Wagner-Meerwein type rearrangement in 5-oxohomoadamantane series.

Efficient methods for introducing various substituents into the α-position of ethyl 5-oxohomoadamantyl-4-carboxylate are reported. An unexpected acid-catalysed 1,2-alkyl shift in the series of synthesized α,α-bis-substituted 5-oxohomoadamantanes, and also in the hydroxy derivatives of homoadamantane was found. Such a retropinacol-like rearrangement leads to tetra- or pentacyclic mono- or bis-lactones containing a homoadamantane moiety.

Molecular design, synthesis and biological evaluation of cage compound-based inhibitors of hepatitis C virus p7 ion channels.

The hepatitis C caused by the hepatitis C virus (HCV) is an acute and/or chronic liver disease ranging in severity from a mild brief ailment to a serious lifelong illness that affects up to 3% of the world population and imposes significant and increasing social, economic, and humanistic burden. Over the past decade, its treatment was revolutionized by the development and introduction into clinical practice of the direct acting antiviral (DAA) agents targeting the non-structural viral proteins NS3/4A, NS5A, and NS5B. However, the current treatment options still have important limitations, thus, the development of new classes of DAAs acting on different viral targets and having better pharmacological profile is highly desirable.