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Updated: Dec 17, 2025
Engineering Antiviral Agents via Surface Plasmon Resonance
Published on: June 14, 2022
Structural Basis of SARS-CoV-2- and SARS-CoV-Receptor Binding and Small-Molecule Blockers as Potential Therapeutics
Hariharan Sivaraman1, Shi Yin Er1, Yeu Khai Choong1
1Department of Biological Sciences, National University of Singapore, Singapore 117543;
Abstract:
Over the past two decades, deadly coronaviruses, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) 2019 pandemic, have majorly challenged public health. The path for virus invasion into humans and other hosts is mediated by host-pathogen interactions, specifically virus-receptor binding. An in-depth understanding of the virus-receptor binding mechanism is a prerequisite for the discovery of vaccines, antibodies, and small-molecule inhibitors that can interrupt this interaction and prevent or cure infection. In this review, we discuss the viral entry mechanism, the known structural aspects of virus-receptor interactions (SARS-CoV-2 S/humanACE2, SARS-CoV S/humanACE2, and MERS-CoV S/humanDPP4), the key protein domains and amino acid residues involved in binding, and the small-molecule inhibitors and other drugs that have (as of June 2020) exhibited therapeutic potential. Specifically, we review the potential clinical utility of two transmembrane serine protease 2 (TMPRSS2)-targeting protease inhibitors, nafamostat mesylate and camostat mesylate, as well as two novel potent fusion inhibitors and the repurposed Ebola drug, remdesivir, which is specific to RNA-dependent RNA polymerase, against human coronaviruses, including SARS-CoV-2.
Insights
Understanding coronavirus entry mechanisms, like SARS-CoV-2 binding to human ACE2, is key for developing effective vaccines and treatments. This review covers viral entry, receptor interactions, and potential therapeutic inhibitors.
Area of Science:
- Virology
- Structural Biology
- Drug Discovery
Background:
- Deadly coronaviruses, including SARS-CoV-2, pose significant public health challenges.
- Host-pathogen interactions, specifically virus-receptor binding, are crucial for viral invasion.
Purpose of the Study:
- To review viral entry mechanisms and structural aspects of virus-receptor interactions.
- To discuss potential therapeutic inhibitors targeting these interactions for coronaviruses.
Main Methods:
- Literature review of viral entry mechanisms.
- Analysis of structural data for SARS-CoV, MERS-CoV, and SARS-CoV-2 receptor binding.
- Review of small-molecule inhibitors and drugs with therapeutic potential.
Main Results:
- Detailed discussion of SARS-CoV-2 S/human ACE2, SARS-CoV S/human ACE2, and MERS-CoV S/human DPP4 interactions.
- Identification of key protein domains and amino acid residues involved in binding.
- Overview of therapeutic agents including protease inhibitors, fusion inhibitors, and remdesivir.
Conclusions:
- Understanding virus-receptor binding is essential for developing countermeasures against coronaviruses.
- Several small-molecule inhibitors and repurposed drugs show promise for treating coronavirus infections.
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