based on the near-identical substrate specificities and high sequence identities (between SARS-CoV-2 and SARS-CoV (86%)), some of the previous progress of specific inhibitors development for the SARS-CoV enzyme can be conferred on its SARS-CoV-2 counterpart: the antivirals ledipasvir or velpatasvir, the drugs Epclusa (velpatasvir/sofosbuvir) and Harvoni (ledipasvir/sofosbuvir) can be effective
combination of thioacetal functional group with decahydroisoquinolin or related fused-ring scaffold would be an approach to design inhibitors for SARS 3CL protease
due to its essential role in processing the polyproteins that are translated from the viral RNA, the enzyme is an attractive drug target among coronaviruses
due to its essential role in processing the polyproteins that are translated from the viral RNA, the enzyme is an attractive drug target among coronaviruses. The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route
prediction of lead molecules which are capable of inhibiting 3C-like protease, and thus inhibit the lifecycle of Middle East Respiratory Syndrome Coronavirus using in silico methods. Detection of potential drugs by structure-based virtual screening and ligand-based virtual screening approach
the use of the deep learning platform Deep Docking in conjunction with a docking program allows rapid estimation of docking scores for 1.3 billion chemical structures into an active site of novel SARS-CoV-2 Mpro. The candidate inhibitors in the top-1000 hit list are chemically diverse, exhibit superior docking scores compared to known protease inhibitors. The structures of the identified compounds are made publicly available should facilitate efforts in rapid development of suitable drug candidates against COVID-19
enzyme undergoes N-terminal and C-terminal autoprocessing using subsite cooperativity. In a dimer of the 3CLpro proform, containing a 10-residue C-terminal prosequence, and the C145A mutation of the catalytic cysteine residue, one of these prosequences is bound, as a substrate, to the active site of a subunit from an adjacent asymmetric unit. Residue Phe at the P3' position is required when the P2 residue is Phe
in full-length inactive 3CLpro with N- and C-terminal extensions as substrates for monitoring self-cleavage, the rate-limiting C-terminal self-cleavage rate of SARS-CoV-2 3CLpro is 35fold faster than that of SARS-CoV 3CLpro using Trx/GST-tagged C145A 3CLpro substrates
in full-length inactive 3CLpro with N- and C-terminal extensions as substrates for monitoring self-cleavage, the rate-limiting C-terminal self-cleavage rate of SARS-CoV-2 3CLpro is 35fold faster than that of SARS-CoV 3CLpro using Trx/GST-tagged C145A 3CLpro substrates
the Vmax of SARS-CoV-2 3CLpro is about 2fold higher than that of SARS-CoV 3CLpro. The proteolytic activity of SARS-CoV-2 3CLpro is slightly more efficient than that of SARS-CoV 3CLpro
the Vmax of SARS-CoV-2 3CLpro is about 2fold higher than that of SARS-CoV 3CLpro. The proteolytic activity of SARS-CoV-2 3CLpro is slightly more efficient than that of SARS-CoV 3CLpro
during the formation of the coronaviral replication/transcription complex, essential steps include processing of the conserved polyprotein nsp7-10 region by the main protease Mpro and subsequent complex formation of the released nsps
the protease 3CLpro processes the polypeptide translation product from the genomic RNA into the structural and nonstructural protein components vital for the replication and packaging of a new generation of viruses
the functional unit of Mpro is a homodimer and each subunit contains a His41-Cys145 catalytic dyad. Presence of a complete substrate-binding pocket and oxyanion hole in both protomers. Reversible substrate-induced dimerization is essential for catalysis, molecular mechanism, overview
the functional unit of Mpro is a homodimer and each subunit contains a His41-Cys145 catalytic dyad. Presence of a complete substrate-binding pocket and oxyanion hole in both protomers. Reversible substrate-induced dimerization is essential for catalysis, molecular mechanism, overview
the overall amino-acid sequence identity of SARS-CoV-2 and SARS-CoV is very high (86%). The conservation is noticeable at the polyprotein cleavage sites. All 11 3CLpro sites are highly conserved or identical, inferring that their respective proteases have very similar specificities. The 3CLpro sequence of SARS-CoV-2 has only 12 out of 306 residues different from that of SARS-CoV (identity = 96%). Conserved sequence identity is detected among all 11 SARS-CoV-2 genomes SARS-CoV-2