Scientists are describing a new type of human zoonotic coronavirus

Recently cell In the study, the researchers described the structure, entry receptors, and antigenicity of a new human coronavirus called CCoV-HuPn-2018 spike glycoprotein. The virus has been identified as recombinant alphacoronavirus in cats and dogs, making zoonotic coronavirus infections more common than previously undiagnosed.

The research: Structure, receptor recognition and antigenicity of human CCoV-HuPn-2018 coronavirus. Photo credit: nawaitgraphic / Shutterstock.com

Background

In the last two decades, the world has experienced a zoonotic outbreak of the beta-coronavirus, which has caused three deaths from animals to humans. These viruses include Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and SARS-CoV-2, the latter of which is responsible for the ongoing coronavirus of 2019 (COVID-19). pandemic.

In Malaysia and the United States, patients with pneumonia and acute respiratory symptoms have been found to have genetically similar variants of coronavirus in dogs and cats. In addition, the new dog-cat recombinant alphacoronavirus CCoV-HuPn-2018 was detected in a patient with pneumonia in Malaysia. These studies suggest that zoonotic coronaviruses transmitted from animal owners to humans may be associated with clinical symptoms.

In the current study, the scientists will describe the structure, input and antigenicity of the newly formed protein CCoV-HuPn-2018.

Structure of CCoV-HuPn-2018 spike glycoprotein

Cryo-electron microscopic findings showed that the trimmer of the spik ectodome contained the N-terminal S1 and the C-terminal S2 subunit. Unit S1 is divided into domain 0 and domain AD, and unit S2 consists of thermonuclear equipment.

Further analysis showed that the spike protein had two different conformations. In one conformation, the domain 0 has left the periphery of the trimmer and is thus called a “output” conformation. In another “proximal” conformation, the domain is directed to the viral membrane.

Dense distribution of oligosaccharides was observed in two spikes. The S1 subunit of CCoV-HuPn-2018 was structurally similar to both HCoV-NL63 and HCoV-229E. However, the S2 subunit of CCoV-HuPn-2018 was structurally similar to the swine epidemic diarrhea virus (PEDV) and feline infectious peritonitis virus (FIPV). These observations suggest that the CCoV-HuPn-2018 protein may be the result of a genetic recombination event.

Similar to coronaviruses of type II cats and dogs, no degradation of polyneuric furine was observed in the S1 / S2 node of the CCoV-HuPn-2018 spik protein. However, a polybasic motive has been identified at the S2 site, which may be related to its division and viral infection.

The mechanism of entry of the virus

The mechanism of entry of CCoV-HuPn-2018 into the host cell was discovered with the help of human erythrocytes. it is in vitro The analysis showed that the 0 domain mediates the process of virus-host-cell merger depending on the sialic acid during virus entry. Aminopeptidase N has been identified as a specific receptor responsible for the entry of CCoV-HuPn-2018.

CCoV-HuPn-2018 was found to interact with aminopeptidase N orthologists in dogs, cats, and pigs to mediate cell entry into the spike protein. However, no interaction was observed between the CCoV-HuPn-2018 spike and the human aminopeptidase N orthologist.

This may be due to the absence of N-linked oligosaccharides in the N position in human aminopeptidase. The introduction of N739 oligosaccharide to the N position of the human aminopeptidase restored its interaction with the CCoV-HuPn-2018 spik protein.

Taken together, these observations suggest that several aminopeptidase orthologists serve as entry receptors for CCoV-HuPn-2018, and that the presence of glycan at position N739 is critical for viral entry processes. Thus, a nucleotide polymorphism may be responsible for the induction of CCoV-HuPn-2018 infection in humans.

antigenicity

CCoV-HuPn-2018 antigenicity was determined by assessing the cross-neutral ability of human plasma infected with endemic alphacoronavirus. Studies have shown that polyclonal antibodies produced by previous exposure to alphacoronavirus can cross-neutralize CCoV-HuPn-2018, but their potency is reduced.

In addition, the monoclonal antibody to swine coronavirus was found to effectively prevent cell entry through the CCoV-HuPn-2018 spike-induced cell by inhibiting the interaction between the CCoV-HuPn-2018 protein and the aminopeptidase N receptor. This finding suggests that the monoclonal antibody to swine coronavirus can be used as a therapeutic intervention against CCoV-HuPn-2018 infection.

Conclusions

Current research suggests that coronavirus transmission from animals to humans may be higher than previously estimated. The results of the study also emphasize the importance of structural and functional characterization of zoonotic pathogens for the development of effective therapy and vaccines.

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