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Published on: November 5, 2021
Current concepts in the development of therapeutics against human and animal coronavirus diseases by targeting NP
Yeu-Yang Tseng1, Guan-Ru Liao2, Abigail Lien3
1WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
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.
Insights
Understanding the coronavirus nucleocapsid (N) protein is crucial for developing broad-spectrum antiviral drugs. This review explores biochemical and structural studies to identify potential N protein antagonists for human and animal coronaviruses.
Area of Science:
- Virology
- Structural Biology
- Drug Discovery
Background:
- Coronaviruses (CoVs) pose significant threats to human and animal health, with recent outbreaks including SARS-CoV, MERS-CoV, and the ongoing COVID-19 pandemic caused by SARS-CoV-2.
- Despite extensive research, effective pharmaceutical interventions for coronavirus diseases remain limited.
- The viral nucleocapsid (N) protein is essential for CoV replication and presents a promising target for therapeutic development.
Purpose of the Study:
- To review current research on the biochemical and structural aspects of the coronavirus N protein.
- To identify potential N protein antagonists as broad-spectrum antiviral agents against both human and animal CoVs.
Main Methods:
- Biochemical and structural studies of the N protein.
- Cell-based assays to evaluate antiviral activity.
- Virtual screening approaches to identify N protein antagonists.
Main Results:
- The N protein's structure and function are key to developing novel inhibitors.
- Identification of potential N protein antagonists through various screening methods.
- Focus on targeting conserved regions of the N protein for broad-spectrum activity.
Conclusions:
- Targeting the coronavirus N protein offers a promising strategy for developing broad-spectrum antiviral therapies.
- Further research into N protein structure-function relationships can accelerate the discovery of effective treatments for CoV infections.
- Identifying N protein antagonists could lead to new interventions against both human and animal coronaviruses.
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Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...

