Recent years have witnessed a remarkable surge in the study of noncovalent interactions andtheir role in diverse areas of chemistry, biology, material science and allied fields. Among all, hydrogenbonding is quite extensively studied. Several other noncovalent interactions continue to attract wide attention.Notably, cation-π interactions play a crucial role in the function of several binding sites, reaction mechanisms,self-assemblies, catalytic mechanisms, adhesion and cohesion properties in many biological andchemical systems. The current review focuses on the character of cation-π interactions, its range and itsoccurrence from a conceptual point of view. The range and nature of cation-π interactions depend on the typeof π-system and cation involved, besides solvent and environment. The size and polarizability of the psystemsand the effective nuclear charge on cation and its multiplicity and spin dictate the structural andenergetic aspects of cation-π interaction. Further, factors affecting the modulation of strength and nature arebrought out in the review. The interplay between the cation-π interaction and the other noncovalent interactions,solvent and counter-ion effects are analysed, and the cooperativity of these forces in organizingsupramolecular architectures are discussed.

How strong is cation-π interaction depends on various factors: It may be weak, medium or strong depending on the nature of cation, π system and environment. The strength of the interaction was shown to alternate a few orders of magnitude depending on the environment.

Exploring the new therapeutic indications of known drugs for treating COVID-19, popularly known as drug repurposing, is emerging as a pragmatic approach especially owing to the mounting pressure to control the pandemic. Targeting multiple targets with a single drug by employing drug repurposing known as the polypharmacology approach may be an optimised strategy for the development of effective therapeutics. In this study, virtual screening has been carried out on seven popular SARS-CoV-2 targets (3CL^pro,PL^pro, RdRp (NSP12), NSP13, NSP14, NSP15, and NSP16). A total of 4015 approved drugs were screened against these targets. Four drugs namely venetoclax, tirilazad, acetyldigitoxin, and ledipasvir have been selected based on the docking score, ability to interact with four or more targets and having a reasonably good number of interactions with key residues in the targets. The MD simulations and MM-PBSA studies showed reasonable stability of protein-drug complexes and sustainability of key interactions between the drugs with their respective targets throughout the course of MD simulations. The identified four drug molecules were also compared with the known drugs namely elbasvir and nafamostat. While the study has provided a detailed account of the chosen protein-drug complexes, it has explored the nature of seven important targets of SARSCoV-2 by evaluating the protein-drug complexation process in great detail.

Drug repurposing strategy against SARS-CoV₂ drug targets. Computational analysis was performed to identify repurposable approved drug candidates against SARS-CoV₂ using approaches such as virtual screening, molecular dynamics simulation and MM-PBSA calculations. Four drugs namely venetoclax, tirilazad, acetyldigitoxin, and ledipasvir have been selected as potential candidates.