Current concepts in the development of therapeutics against human and animal coronavirus diseases by targeting NP

Yeu-Yang Tseng; Guan-Ru Liao; Abigail Lien; Wei-Li Hsu

doi:10.1016/j.csbj.2021.01.032

Current concepts in the development of therapeutics against human and animal coronavirus diseases by targeting NP

Comput Struct Biotechnol J. 2021:19:1072-1080. doi: 10.1016/j.csbj.2021.01.032. Epub 2021 Jan 30.

Authors

Yeu-Yang Tseng¹, Guan-Ru Liao², Abigail Lien³, Wei-Li Hsu²

Affiliations

¹ WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
² Graduate Institute of Microbiology and Public Health, National Chung Hsing University, Taiwan.
³ Department of Biochemistry, University of Washington, Seattle, USA.

Abstract

The coronavirus (CoV) infects a broad range of hosts including humans as well as a variety of animals. It has gained overwhelming concerns since the emergence of deadly human coronaviruses (HCoVs), severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, followed by Middle East respiratory syndrome coronavirus (MERS-CoV) in 2015. Very recently, special attention has been paid to the novel coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 due to its high mobility and mortality. As the COVID-19 pandemic continues, despite vast research efforts, the effective pharmaceutical interventions are still not available for clinical uses. Both expanded knowledge on structure insights and the essential function of viral nucleocapsid (N) protein are key basis for the development of novel, and potentially, a broad-spectrum inhibitor against coronavirus diseases. This review aimed to delineate the current research from the perspective of biochemical and structural study in cell-based assays as well as virtual screen approaches to identify N protein antagonists targeting not only HCoVs but also animal CoVs.

Keywords: AMP, UMP, GMP and CMP, ribonucleoside 5′-monophosphates; Antagonists; BCoV, bovine coronavirus; CCoV, canine coronavirus; COVID-19; COVID-19, coronavirus disease 2019; CTD, C-terminus dimerization domain; CoV, coronavirus; Coronavirus; E, envelope protein; ECoV, equine coronavirus; FECV, feline enteric coronavirus; FIPV, feline infectious peritonitis virus; HCoVs, human coronaviruses; HIV, human immunodeficiency virus; IBV, infectious bronchitis virus; IFN, interferon; Inhibitors; MERS-CoV, Middle East respiratory syndrome coronavirus; MHV, mouse hepatitis virus; MP, membrane protein; N protein; NTD, N-terminus RNA-binding domain; PDCoV, porcine deltacoronavirus; PEDV, Porcine epidemic diarrhea virus; PRCV, porcine respiratory coronavirus; RBD, RNA-binding domain; RNP, ribonucleoproteins; SARS-CoV, severe acute respiratory syndrome coronavirus; SARS-CoV-2; SP, spike protein; SeCoV, swine enteric coronavirus; TCoV, turkey coronavirus; TGEV, transmissible gastroenteritis virus; nsp3, the nonstructural protein 3; shRNAs, short hairpin RNAs; siRNA, small interfering RNA.

Publication types

Review