#Genomic and structural #evidence of #SARS-CoV-2 and #MERS-CoV in migratory #birds

 

Significance

Coronaviruses are regarded as highly important pathogens of birds and mammals. Herein, we obtained three almost full-length severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes and one partial Middle East respiratory syndrome coronavirus (MERS-CoV) genome in the feces of migratory birds based on meta-transcriptome and PCR amplification. We determined the affinities and the complex structures between receptor-binding domain (RBD) of the SARS-CoV-2 viral spike protein and angiotensin-converting enzyme 2 (ACE2) protein of two migratory birds, Tundra and Black swans. Moreover, pseudotyped SARS-CoV-2 variants can enter into HeLa cells expressing ACE2 proteins of these birds. Altogether, our results expand our understanding of migratory birds as potential carrier of both SARS-CoV-2 and MERS-CoV.

Abstract

Migratory birds are the natural reservoir of influenza A virus (IAV), but their role as a carrier of SARS-CoV-2 remains unclear. Here, we report the identification of three almost full-length viral genome sequences of SARS-CoV-2 variants of concern (VOCs) in Tundra swans. These sequences are named hCoV-19/Tundra swan/Jiangxi/IMCAS_M1/2021 (IMCAS_M1), hCoV-19/Tundra swan/Jiangxi /IMCAS_M2/2021 (IMCAS_M2), and hCoV-19/Tundra swan/Jiangxi/IMCAS_M3/2021 (IMCAS_M3). IMCAS_M1 and IMCAS_M3 have the same mutations as the Beta VOC (K417N, E484K, and N501Y) in the receptor-binding domain (RBD) of the viral spike (S) protein, whereas IMCAS_M2 shares the same mutations as the Gamma VOC (K417T, E484K, and N501Y) in the RBD with all three showing their distinct mutations in the genomes. Virus receptor angiotensin-converting enzyme 2 (ACE2) proteins from both Tundra swan (tsACE2) and Black swan (bsACE2) can bind to the RBDs of all three viruses and the Alpha VOC, but not to RBD of the prototype (PT) virus. The polar contacts and hydrophobic interactions revealed by cryo-electron microscopy (cryo-EM) structures of the RBD–ACE2 complex, play key roles in virus–receptor engagement. Furthermore, HeLa cells expressing bsACE2 and tsACE2 proteins could be transduced by pseudotyped SARS-CoV-2 variants (Alpha, Beta, and Gamma) but not PT SARS-CoV-2. In addition, we obtained one partial genome of MERS-CoV named Bar-headed goose/Tibet/IMCAS_M4/2022 (IMCAS_M4) with 20,180 bp (~70.0% coverage). Our findings highlight the importance of migratory birds as potential carrier of both SARS-CoV-2 and MERS-CoV, thereby posing potential threat to public health.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://www.pnas.org/

Link: https://www.pnas.org/doi/10.1073/pnas.2400023123

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