To determine whether antiviral drugs can effectively inhibit HCoV-OC43 replication in HCOs and whether anti-inflammatory drugs can prevent the inflammatory response and cellular damage post-infection, we tested antiviral drugs along with two compounds targeting the TNF pathway, either alone or in combination: (1) necrostatin-1 (NEC-1), an RIP1-targeted inhibitor of TNF-induced necroptosis. Here, PCSK1 is linked to infection.