Steps in coronavirus replication that are potential targets for antiviral drugs and vaccines. The spike glycoprotein S is a good candidate for vaccines because neutralizing antibodies are directed against S. Blockade of the specific virus receptor on the surface of the host cell by monoclonal antibodies or other ligands can prevent virus entry. Receptor-induced conformational changes in the S protein can be blocked by peptides that inhibit membrane fusion and virus entry. The polyprotein of the replicase protein is cleaved into functional units by virus-encoded proteinases. Protease inhibitors may block replication. The polymerase functions in a unique membrane-bound complex in the cytoplasm, and the assembly and functions of this complex are potential drug targets. Viral mRNAs made by discontinuous transcription are shown in the cytoplasm with the protein that each encodes indicated at the right. The common 70 base long leader sequence on the 5′ end of each mRNA is shown in red. Budding and exocytosis are processes essential to virus replication that may be targets for development of antiviral drugs. M, membrane protein required for virus budding; S, viral spike glycoprotein that has receptor binding and membrane fusion activities; E, small membrane protein that plays a role in coronavirus assembly; N, nucleocapsid phosphoprotein associated with viral RNA inside the virion. Adapted with permission from ref. 35.