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Inhibition of Human Coronaviruses by Piperidine-4-Carboxamides

Immunization efforts for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been successful in reducing disease severity. Yet new variants continue to emerge, as well as vaccine hesitancy from some, requiring ongoing efforts to identify antiviral agents for SARS-CoV-2 treatment. Here, we evaluated the in vitro activities of piperidine-4-carboxamide compound (NCGC2955) against human α- coronavirus NL63, β-coronaviruses OC43, and the alpha and delta variants of SARS-CoV-2 in several cell lines. NCGC2955 showed antiviral activity in NL63-infected Vero and MK2 cells: EC 50 2.5± 0.15 µM and 1.5 ± 0.2 µM, respectively. The cellular toxicity in both cell types was > 300 µM. The EC 50 of NCGC2955 in OC43-infected human foreskin fibroblasts was 1.5 ± 0.01 µM, and a dose-response in reducing OC43 antigen was observed in Western blot analysis. NCGC2955 inhibited SARS-CoV-2 in both Vero E6 and Calu-3 cells. A comparison of the activity of NCGC2955 and a structurally related analog (153) in SARS-CoV-2-infected Calu-3 cells revealed similar EC 50 (0.2 ± 0.02 µM and 0.11 ± 0.04 µM, respectively). Both compounds inhibited the delta variant in Calu-3 cells. This class of agents may be promising broad-spectrum antivirals that can be further developed for clinical use.