Discovery of New Potent anti-MERS CoV Fusion Inhibitors

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV), capable of zoonotic transmission, has been associated with emerging viral pneumonia in humans. In this study, a set of highly potent peptides were designed to prevent MERS-CoV fusion through competition with heptad repeat domain 2 (HR2) at its HR1 binding site. We designed eleven peptides with stronger estimated HR1 binding affinities than the wild-type peptide to prevent viral fusion with the cell membrane. Eight peptides showed strong inhibition of spike-mediated MERS-CoV cell-cell fusion with IC50 values in the nanomolar range (0.25–2.3 µM). Peptides #4–6 inhibited 95–98.3% of MERS-CoV plaque formation. Notably, peptide four showed strong inhibition of MERS-CoV plaques formation with EC50 = 0.302 µM. All peptides demonstrated safe profiles without cytotoxicity up to a concentration of 10 μM, and this cellular safety, combined with their anti-MERS-CoV antiviral activity, indicate all peptides can be regarded as potential promising antiviral agents.

Omicron variant genome evolution and phylogenetics

“…Bioinformatics and phylogeny tools are gold standards in microbial evolution and drug discovery against selected molecular targets. 8 , 9 , 10 Analysis of SARS‐CoV‐2 genome constituents highlighted the forces affecting virus evolution. 11 In this study, we used a combination of tools to get insights into the evolution of Omicron variant.…”

Drug Discovery of New Anti-Inflammatory Compounds by Targeting Cyclooxygenases

“…Therapeutic development will continue to rely extensively on computational tools to aid in the identification and validation of potential drug targets, which will help to accelerate the process [ 13 , 14 , 15 , 16 ]. The field of bioinformatics is at the forefront of our efforts to better comprehend the workings of the cell.…”

Omicron variant receptor-binding domain phylogenetics and molecular dynamics

“…Bioinformatics and phylogenetic analyses are gold standards in the study of microbial evolution and the development of novel therapeutics targeting specific biological targets [ [19] , [20] , [21] ]; we used a variety of these techniques to gain insights into the evolution of the Omicron variant RBD. Two methods we used to construct a phylogenetic tree are UPGMA and NJ.…”