Identification of SARS-CoV-2 Papain-like Protease (PLpro) Inhibitors Using Combined Computational Approach

In the currentpandemic,findingan effectivedrugto preventortreatthe infectionis the highestpriority.A rapidand safeapproachto counteractCOVID-19is in silicodrugrepurposing.The SARS-CoV-2PLpropromotesviral replicationand modu-latesthe hostimmunesystem,resultingin inhibitionof thehostantiviralinnateimmuneresponse,and thereforeis anattractivedrugtarget.In this study,we useda combinedinsilicovirtualscreeningfor candidatesfor SARS-CoV-2PLproproteaseinhibitors.We usedthe Informationalspectrummethodappliedfor SmallMoleculesfor searchingthe Drugbankdatabasefollowedby moleculardocking.Afterin silicoscreen-ing of drugspace,we identified44 drugsas potentialSARS-CoV-2PLproinhibitorsthat we proposefor furtherexperimentaltesting.A previous version of this manuscript has been deposited on a preprint server: [https://doi.org/10.33774/chemrxiv-2021-39cd6-v2