Related Experiment Video
Updated: Nov 27, 2025
Engineering Antiviral Agents via Surface Plasmon Resonance
Published on: June 14, 2022
Key residues influencing binding affinities of 2019-nCoV with ACE2 in different species
Senbiao Fang1, Ruoqian Zheng1, Chuqi Lei2
1Xiangtan University, Xiangtan, China.
Abstract:
The Novel Coronavirus Disease 2019 (COVID-19) has become an international public health emergency, which poses the most serious threat to the human health around the world. Accumulating evidences have shown that the new coronavirus could not only infect human beings, but also can infect other species which might result in the cross-species infections. In this research, 1056 ACE2 protein sequences are collected from the NCBI database, and 173 species with >60% sequence identity compared with that of human beings are selected for further analysis. We find 14 polar residues forming the binding interface of ACE2/2019-nCoV-Spike complex play an important role in maintaining protein-protein stability. Among them, 8 polar residues at the same positions with that of human ACE2 are highly conserved, which ensure its basic binding affinity with the novel coronavirus. 5 of other 6 unconserved polar residues (positions at human ACE2: Q24, D30, K31, H34 and E35) are proved to have an effect on the binding patterns among species. We select 21 species keeping close contacts with human beings, construct their ACE2 three-dimensional structures by Homology Modeling method and calculate the binding free energies of their ACE2/2019-nCoV-Spike complexes. We find the ACE2 from all the 21 species possess the capabilities to bind with the novel coronavirus. Compared with the human beings, 8 species (cow, deer, cynomys, chimpanzee, monkey, sheep, dolphin and whale) present almost the same binding abilities, and 3 species (bat, pig and dog) show significant improvements in binding affinities. We hope this research could provide significant help for the future epidemic detection, drug and vaccine development and even the global eco-system protections.
Insights
The novel coronavirus can infect many species by binding to ACE2 proteins. Conserved residues ensure basic binding, while others affect cross-species infection potential, aiding in epidemic detection and vaccine development.
Area of Science:
- Biochemistry
- Virology
- Comparative Genomics
Background:
- The COVID-19 pandemic highlights the zoonotic potential of coronaviruses.
- Understanding cross-species transmission is crucial for public health and pandemic preparedness.
- The Angiotensin-Converting Enzyme 2 (ACE2) receptor is a key host factor for SARS-CoV-2 entry.
Purpose of the Study:
- To investigate the binding affinity of the novel coronavirus (SARS-CoV-2) spike protein to ACE2 receptors across different species.
- To identify key amino acid residues in ACE2 that mediate viral binding and influence cross-species infections.
- To assess the potential for zoonotic transmission and inform strategies for epidemic control.
Main Methods:
- Collected 1056 ACE2 protein sequences from NCBI database.
- Selected 173 species with >60% sequence identity to human ACE2 for analysis.
- Identified 14 polar residues at the ACE2/SARS-CoV-2 spike protein binding interface.
- Constructed 3D ACE2 structures for 21 species using Homology Modeling.
- Calculated binding free energies for ACE2/SARS-CoV-2 spike protein complexes.
Main Results:
- Identified 14 critical polar residues at the ACE2 binding interface, with 8 being highly conserved across species.
- Found that 5 unconserved polar residues significantly influence interspecies binding patterns.
- All 21 analyzed species showed ACE2 capability to bind SARS-CoV-2 spike protein.
- Eight species exhibited binding affinities similar to humans, while bats, pigs, and dogs showed enhanced binding.
Conclusions:
- Conserved residues in ACE2 are essential for basic binding affinity to SARS-CoV-2.
- Variations in specific ACE2 residues modulate binding affinities across species, impacting zoonotic potential.
- This research provides insights for epidemic surveillance, antiviral drug development, and vaccine design.
Related Concept Videos
01:49Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
02:50Conjugated Proteins
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...
01:16Protein-Drug Binding: Mechanism and Kinetics
Various forces drive these interactions, including hydrogen bonds, hydrophobic interactions, ionic bonds, electrostatic interactions, and van der Waals forces. These bonds enable drugs to bind to specific sites on proteins,...
00:49Ligand Binding and Linkage
02:28Leaky Scanning
01:20Factors Affecting Protein-Drug Binding: Protein-Related Factors
The physicochemical properties of a drug play a significant role in its ability to bind to proteins. Lipophilic drugs, which dissolve in fats, oils, and lipids, can be...