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.

Computer-aided Design of Wide-spectrum Coronavirus Helicase NSP13 Cage Inhibitors: A Molecular Modelling Approach.

Background: The coronavirus helicase NSP13 plays a critical role in its life cycle. The found NSP13 inhibitors have been tested only in vitro but they definitely have the potential to become antiviral drugs. Thus, the search for NSP13 inhibitors is of great importance.

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.

Catalyst-free formal [3 + 2] cycloaddition of stabilized ,-cyclic azomethine imines to 3-nitrobenzofurans and 3-nitro-4-chromenes: access to heteroannulated pyrazolo[1,2-]pyrazoles.

We have studied the [3 + 2]-cycloaddition of various ,-cyclic azomethine imines to 3-nitrobenzofurans. This process is a rare example of their dearomatization. We have also extended this process to the related 3-nitro-4-chromenes as dipolarophiles.

Adamantane derivatives as potential inhibitors of p37 major envelope protein and poxvirus reproduction. Design, synthesis and antiviral activity.

Currently, smallpox, caused by the variola virus belonging to the poxvirus family, has been completely eradicated according to the WHO. However, other representatives of poxviruses, such as vaccinia virus, cowpox virus, ectromelia virus, monkeypox virus, mousepox virus and others, remain in the natural environment and can infect both animals and humans. The pathogens of animal diseases, belonging to the category with a high epidemic risk, have already caused several outbreaks among humans, and can, in an unfavorable combination of circumstances, cause not only an epidemic, but also a pandemic.

Heterocyclic Inhibitors of Viroporins in the Design of Antiviral Compounds.

Ion channels of viruses (viroporins) represent a common type of protein targets for drugs. The relative simplicity of channel architecture allows convenient computational modeling and enables virtual search for new inhibitors. In this review, we analyze the data published over the last 10 years on known ion channels of viruses that cause socially significant diseases.

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.

Design of Broad-Spectrum Inhibitors of Influenza A Virus M2 Proton Channels: A Molecular Modeling Approach.

Background: The influenza A virus M2 proton channel plays a critical role in its life cycle. However, known M2 inhibitors have lost their clinical efficacy due to the spread of resistant mutant channels. Thus, the search for broad-spectrum M2 channel inhibitors is of great importance.