Related Experiment Video
Updated: Jun 28, 2026
05:50
Pharmacophore Modeling for Targets with Extensive Ligand Libraries: A Case Study on SARS-CoV-2 Mpro
Published on: September 26, 2025
Screening candidate intermediate hosts for porcine respiratory coronavirus using molecular docking
Rochanawan Sootichote1, Aekkapot Chamkasem2, Waraphan Toniti3
1Center of Excellence for Antibody Research, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
Summary
Porcine Respiratory Coronavirus (PRCoV) can adapt to bind human receptors. Minimal genetic changes in viral receptor-binding domains (RBDs) can enhance binding to human Aminopeptidase N (APN), suggesting zoonotic spillover risks.
Area of Science:
- Virology
- Molecular Biology
- Structural Biology
- Evolutionary Biology
Background:
- Emerging coronaviruses cause significant global health and economic disruption due to zoonotic spillover.
- Cross-species viral transmission depends on interactions between viral receptor-binding domains (RBDs) and host cellular receptors.
- Porcine Respiratory Coronavirus (PRCoV) and its interaction with Aminopeptidase N (APN) serve as a model for studying host adaptation.
Purpose of the Study:
- To investigate host adaptation mechanisms of PRCoV by analyzing its RBD interaction with APN across diverse vertebrate species.
- To evaluate the potential for PRCoV to adapt and bind to human APN (hAPN), assessing zoonotic spillover risks.
Main Methods:
- Sequence analysis of APN proteins from 18 vertebrate species to determine similarity with porcine APN (pAPN).
- Molecular docking simulations to estimate binding affinity between PRCoV RBD and various host APN proteins.
- Structural analysis of RBD-APN interactions and assessment of binding affinity changes with specific amino acid substitutions.
Main Results:
- Camelidae, Bovidae, and Hipposiderid bats showed high sequence similarity (70%-85%) to pAPN. Hipposiderid bats exhibited significant similarity to both pAPN and hAPN.
- Molecular docking predicted high receptor compatibility between PRCoV RBD and APN from pigs, cats, bats, horses, rabbits, and cattle.
- Wild-type PRCoV had a tenfold lower binding affinity for hAPN than pAPN, but specific single amino acid substitutions in the RBD dramatically enhanced hAPN binding (Kd < 100 pM).
Conclusions:
- Minimal genetic modifications in the PRCoV RBD can significantly enhance binding to hAPN, indicating a potential pathway for zoonotic transmission.
- The study highlights the importance of host receptor diversity and viral evolution monitoring for early detection of potential pandemic threats.
- Findings support receptor-based surveillance strategies and underscore the need for further validation of in-silico predictions for emerging infectious diseases.
