TY - JOUR
T1 - Docking simulations exhibit bortezomib and other boron-con-taining peptidomimetics as potential inhibitors of sars-cov-2 main protease
AU - Vega-Valdez, Iván R.
AU - Rosalez, Melvin N.
AU - Santiago-Quintana, José M.
AU - Farfán-García, Eunice D.
AU - Soriano-Ursúa, Marvin A.
N1 - Publisher Copyright:
© 2020 Bentham Science Publishers.
PY - 2020
Y1 - 2020
N2 - Background: Treatment of the COVID19 pandemic requires drug de-velopment. Boron-containing compounds are attractive chemical agents, some of them act as proteases inhibitors. Objective: The present study explores the role of boronic moieties in molecules interacting on the binding site of the SARS-CoV-2 main protease. Methods: Conventional docking procedure was applied by assaying boron-free and boron-containing compounds on the recently reported crystal structure of SARS-CoV-2 main protease (PDB code: 6LU7). The set of 150 ligands includes bortezomib and inhibitors of coronavirus proteases. Results: Most of the tested compounds share contact with key residues and pose on the cleavage pocket. The compounds with a boron atom in their structure are often estimated to have higher affinity than boron-free analogues. Conclusion: Interactions and the affinity of boron-containing peptidomimetics strongly suggest that boron-moieties increase affinity on the main protease, which is tested by in vitro assays. A Bis-boron-containing compound previously tested active on SARS-virus protease and bortezomib were identified as potent li-gands. These advances may be relevant to drug designing, in addition to testing available boron-containing drugs in patients with COVID19 infection.
AB - Background: Treatment of the COVID19 pandemic requires drug de-velopment. Boron-containing compounds are attractive chemical agents, some of them act as proteases inhibitors. Objective: The present study explores the role of boronic moieties in molecules interacting on the binding site of the SARS-CoV-2 main protease. Methods: Conventional docking procedure was applied by assaying boron-free and boron-containing compounds on the recently reported crystal structure of SARS-CoV-2 main protease (PDB code: 6LU7). The set of 150 ligands includes bortezomib and inhibitors of coronavirus proteases. Results: Most of the tested compounds share contact with key residues and pose on the cleavage pocket. The compounds with a boron atom in their structure are often estimated to have higher affinity than boron-free analogues. Conclusion: Interactions and the affinity of boron-containing peptidomimetics strongly suggest that boron-moieties increase affinity on the main protease, which is tested by in vitro assays. A Bis-boron-containing compound previously tested active on SARS-virus protease and bortezomib were identified as potent li-gands. These advances may be relevant to drug designing, in addition to testing available boron-containing drugs in patients with COVID19 infection.
KW - Boron
KW - Boronic acids
KW - Bortezomib
KW - COVID19
KW - Oligopeptides
KW - Protease inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85101118007&partnerID=8YFLogxK
U2 - 10.2174/2212796814999201102195651
DO - 10.2174/2212796814999201102195651
M3 - Artículo
AN - SCOPUS:85101118007
SN - 2212-7968
VL - 14
SP - 279
EP - 288
JO - Current Chemical Biology
JF - Current Chemical Biology
IS - 4
ER -