New developments for the design, synthesis and biological evaluation of potent SARS-CoV 3CLpro inhibitors

TL;DR: This review highlights past and present drug discovery and medicinal‐chemistry approaches against SARS‐CoV, MERS‐coV and COVID‐19 targets and hopes to stimulate further research and will be a useful guide to the development of effective therapies against CO VID‐19 and other pathogenic coronaviruses.

TL;DR: 16-(R) is a noncovalent SARS-CoV 3CL Pro inhibitor with moderate MW and good enzyme and antiviral inhibitory activity and provides an excellent starting point for the further design and refinement of 3CLpro inhibitors that act by a non covalent mechanism of action.

TL;DR: Structural-activity analysis showed that catechol and α,β-unsaturated carbonyl moiety in the molecule were the key requirement for SARS-CoV cysteine protease inhibition.

TL;DR: All quinone-methide triterpenes 1–4 have proven to be competitive by the kinetic analysis and show potent inhibitory activities in A-ring and more hydrophobic E-ring assist to exhibit potent activity.

TL;DR: A novel coronavirus is associated with this outbreak of severe acute respiratory syndrome, and the evidence indicates that this virus has an etiologic role in SARS.

TL;DR: Phylogenetic analyses and sequence comparisons showed that SARS-CoV is not closelyrelated to any of the previouslycharacterized coronaviruses.

TL;DR: Molecular modeling suggests that available rhinovirus 3Cpro inhibitors may be modified to make them useful for treating SARS, and a homology model for SARS coronavirus (SARS-CoV) Mpro is constructed.

TL;DR: The spike protein showed the strongest initial responses to positive selection pressures, followed by subsequent purifying selection and eventual stabilization, and major deletions were observed in the Orf8 region of the genome at the start and the end of the epidemic.