Inhibition of Human Coronaviruses by Piperidine-4-Carboxamides

28 Pages Posted: 3 Mar 2022

See all articles by Xin Guo

Xin Guo

Medical College of Wisconsin

Ayan Kumar Ghosh

Medical College of Wisconsin

Halli Miller

Medical College of Wisconsin

Konstance Knox

Coppe Healthcare Solutions, Inc.

Madhuchhanda Kundu

Coppe Healthcare Solutions, Inc.

Francis Peterson

Medical College of Wisconsin

David J. Meyers

affiliation not provided to SSRN

Ravit Arav-Boger

Medical College of Wisconsin

Abstract

Immunization efforts for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been successful in reducing disease severity. However, as the pandemic continues and new variants emerge, along with vaccine hesitancy, efforts are ongoing 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: EC50 2.5± 0.15 µM and 1.5 ± 0.2 µM, respectively. The cellular toxicity in both cell types was > 300 µM. The EC50 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 SARS26 CoV-2 in both Vero E6 and Calu-3 cells. A comparison of the activity of NCGC2955 and a structurally related analog (153) in SARS27 CoV-2-infected Calu-3 cells revealed similar EC50 (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 towards clinical use.

Note:
Funding: JM acknowledges funding from Flight Attendant Medical Research Institute (FAMRI) and Institute for Clinical and Translational Research UL1TR003098.

Declaration of Interests: None to declare.

Keywords: coronaviruses, SARS-CoV-2, piperidine-4-carboxamide

Suggested Citation

Guo, Xin and Ghosh, Ayan Kumar and Miller, Halli and Knox, Konstance and Kundu, Madhuchhanda and Peterson, Francis and Meyers, David J. and Arav-Boger, Ravit, Inhibition of Human Coronaviruses by Piperidine-4-Carboxamides. Available at SSRN: https://ssrn.com/abstract=4032380 or http://dx.doi.org/10.2139/ssrn.4032380

Xin Guo

Medical College of Wisconsin ( email )

8701 Watertown Plank Road
Milwaukee, WI WI 53226
United States

Ayan Kumar Ghosh

Medical College of Wisconsin ( email )

8701 Watertown Plank Road
Milwaukee, WI WI 53226
United States

Halli Miller

Medical College of Wisconsin ( email )

8701 Watertown Plank Road
Milwaukee, WI WI 53226
United States

Konstance Knox

Coppe Healthcare Solutions, Inc. ( email )

W229N1870 Westwood Dr
Waukesha, WI 53186
United States

Madhuchhanda Kundu

Coppe Healthcare Solutions, Inc. ( email )

W229N1870 Westwood Dr
Waukesha, WI 53186
United States

Francis Peterson

Medical College of Wisconsin ( email )

8701 Watertown Plank Road
Milwaukee, WI WI 53226
United States

David J. Meyers

affiliation not provided to SSRN ( email )

No Address Available

Ravit Arav-Boger (Contact Author)

Medical College of Wisconsin ( email )

8701 Watertown Plank Road
Milwaukee, WI WI 53226
United States

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