Molecular dynamic study of SARS-CoV-2 with various S protein mutations and their effect on thermodynamic properties.

Studying the structure of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein is important to understand the infection process. The S protein is necessary in completing the virus life cycle and is responsible for the appearance of new variants and drug and vaccine resistance. Understanding the structure and dynamics of biological macromolecules is essential for understanding how they function. In this work, we investigated the effects of mutations on S protein stability and solubility through molecular dynamic (MD) simulation in a 100 ns (ns) period. We screened four variants in addition to the wild type (WT). Results show that changes on MD simulation parameters of S protein indicate fluctuations and changes in the conformation, especially in the area between 300 and 600 amino acids (aa). This provides us an image of how the virus protein can reshape itself to adapt to any changes that occur in human angiotensin-converting enzyme 2 or drugs that can target the protein region. Our results also show that the Brazil variant has high fluctuations and unstable folding at some stages compared with other variants.

Repurposing benzimidazole and benzothiazole derivatives as potential inhibitors of SARS-CoV-2: DFT, QSAR, molecular docking, molecular dynamics simulation, and in-silico pharmacokinetic and toxicity studies.

Density Functional Theory (DFT) and Quantitative Structure-Activity Relationship (QSAR) studies were performed on four benzimidazoles (compounds 1-4) and two benzothiazoles (compounds 5 and 6), previously synthesized by our group. The compounds were also investigated for their binding affinity and interactions with the SARS-CoV-2 Mpro (PDB ID: 6LU7) and the human angiotensin-converting enzyme 2 (ACE2) receptor (PDB ID: 6 M18) using a molecular docking approach. Compounds 1, 2, and 3 were found to bind with equal affinity to both targets. Compound 1 showed the highest predictive docking scores, and was further subjected to molecular dynamics (MD) simulation to explain protein stability, ligand properties, and protein-ligand interactions. All compounds were assessed for their structural, physico-chemical, pharmacokinetic, and toxicological properties. Our results suggest that the investigated compounds are potential new drug leads to target SARS-CoV-2.

In the face of the future, what do we learn from COVID-19?

Coronavirus disease (COVID-19) is a highly contagious infection caused by a recently identified coronavirus. The first known case was discovered in December 2019 in Wuhan, China. Since then, the illness has spread globally, resulting in an ongoing epidemic. Here, we would like to address one of the most pressing and outstanding questions which rise about COVID-19 during the year and a half since its discovery: what have we learned from COVID-19?