Compounds and treatment methods with compounds exhibiting antiviral activity and/or inhibition of viral replication against viruses, particularly those belonging to the picornaviru s -like supercluster, including coronavirus having a formula: (I) or a prodrug or pharmaceutically-acceptable salt thereof, where: each X comprises at least one cyclic moiety directly attached to the oxygen or connected via an alkyl linkage, where at least one of the linkage and/or the X moiety comprises a deuterium substitution; and Z is selected from the group consisting of aldehydes and bisulfite salts, or the ester or carbamate prodrugs thereof.