How helpful were molecular dynamics simulations in shaping our understanding of SARS-CoV-2 spike protein dynamics?

The SARS-CoV-2 spike protein (S) represents an important viral component that is required for successful viral infection in humans owing to its essential role in recognition of and entry to host cells. The spike is also an appealing target for drug designers who develop vaccines and antivirals. This article is important as it summarizes how molecular simulations successfully shaped our understanding of spike conformational behavior and its role in viral infection.

The discovery of novel antivirals for the treatment of mpox: is drug repurposing the answer?

Introduction: Drugs that have demonstrated good activity against any member of the Orthopoxvirus genus are good candidates for repurposing studies against the mpox virus (MPXV). The conserved biology of poxviruses has proven beneficial from a clinical virology perspective. Evolutionarily conserved proteins tend to function in a highly similar way.

Novel inhibitors against wild-type and mutated HCV NS3 serine protease: an in silico study.

In 2011, the FDA approved boceprevir as a hepatitis C virus (HCV) NS3 serine protease inhibitor. The sustained virological response rate for treatment with this approved compound is considerably low. Patients have not responded as much as expected to boceprevir therapy.

A comparative study of the efficiency of HCV NS3/4A protease drugs against different HCV genotypes using in silico approaches.

Aims: To investigate the efficacy of Direct Acting Antivirals (DAAs) in the treatment of different Hepatitis C Virus (HCV) genotypes.

Main Methods: Homology modeling is used to predict the 3D structures of different genotypes while molecular docking is employed to predict genotype - drug interactions (Binding Mode) and binding free energy (Docking Score).

Key Findings: Simeprevir (TMC435) and to a lesser degree MK6325 are the best drugs among the studied drugs.

Molecular docking investigation of the binding interactions of macrocyclic inhibitors with HCV NS3 protease and its mutants (R155K, D168A and A156V).

Hepatitis C Virus (HCV) non-structural protein 3 (NS3) protease drug resistance poses serious challenges on the design of an effective treatment. Substrate Envelope Hypothesis, "the substrates of HCV NS3/4A protease have a consensus volume inside the active site called substrate envelope" is used to design potent and specific drugs to overcome this problem. Using molecular docking, we studied the binding interaction of the different inhibitors and protein and evaluated the effect of three different mutations (R155K, D168A and A156V) on the binding of inhibitors.

QSAR analysis and molecular docking simulation of suggested peptidomimetic NS3 protease inhibitors.

Based on the N-terminal hexapeptide product of hydrolysis (EDVVCC) at HCV NS5A/5B junction, three modified groups of compounds are built. The first group contains linear peptides while the second and third groups contain P1-P3 and P2-P4 macrocyclic structures, respectively. Quantitative Structure Activity Relationship (QSAR) characterization and docking simulations are performed in order to investigate the potential of these compounds as HCV NS3/4A protease inhibitors.