#Comparison of #SARS-CoV-2 #spike protein binding to #ACE2 #receptors from #human, #pets, farm #animals, and putative intermediate hosts (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Comparison of SARS-CoV-2 spike protein binding to ACE2 receptors from human, pets, farm animals, and putative intermediate hosts

Xiaofeng Zhai, Jiumeng Sun, Ziqing Yan, Jie Zhang, Jin Zhao, Zongzheng Zhao, Qi Gao, Wan-Ting He, Michael Veit, Shuo Su

DOI: 10.1128/JVI.00831-20



The emergence of a novel coronavirus, SARS-CoV-2, resulted in a pandemic. Here, we used X-ray structures of human ACE2 bound to the receptor-binding domain (RBD) of the spike protein (S) from SARS-CoV-2 to predict its binding to ACE2 proteins from different animals, including pets, farm animals, and putative intermediate hosts of SARS-CoV-2. Comparing the interaction sites of ACE2 proteins known to serve or not serve as receptor allows to define residues important for binding. From the 20 amino acids in ACE2 that contact S up to seven can be replaced and ACE2 can still function as the SARS-CoV-2 receptor. These variable amino acids are clustered at certain positions, mostly at the periphery of the binding site, while changes of the invariable residues prevent S-binding or infection of the respective animal. Some ACE2 proteins even tolerate the loss or the acquisition of N-glycosylation sites located near the S-interface. Of note, Pigs and dogs, which are not or not effectively infected and have only a few changes in the binding site, exhibit relatively low levels of ACE2 in the respiratory tract. Comparison of the RBD of S of SARS-CoV-2 with viruses from Bat-CoV-RaTG13 and Pangolin-CoV revealed that the latter contains only one substitution, whereas the Bat-CoV-RaTG13 exhibits five. However, ACE2 of pangolin exhibit seven changes relative to human ACE2, a similar number of substitutions is present in ACE2 of bats, raccoon, and civet suggesting that SARS-CoV-2 may not especially adapted to ACE2 of any of its putative intermediate hosts. These analyses provide new insight into the receptor usage and animal source/origin of SARS-CoV-2.



SARS-CoV-2 is threatening people worldwide and there are no drugs or vaccines available to mitigate its spread. The origin of the virus is still unclear and whether pets and livestock can be infected and transmit SARS-CoV-2 are important and unknown scientific questions. Effective binding to the host receptor ACE2 is the first prerequisite for infection of cells and determines the host range. Our analysis provides a framework for the prediction of potential hosts of SARS-CoV-2. We found that ACE2 from species known to support SARS-CoV-2 infection tolerate many amino acid changes indicating that the species barrier might be low. An exception are dogs and especially pigs, which, however, revealed relatively low ACE2 expression levels in the respiratory tract. Monitoring of animals is necessary to prevent the generation of a new coronavirus reservoir. Finally, our analysis also showed that SARS-CoV-2 may not be specifically adapted to any of its putative intermediate hosts.

Copyright © 2020 American Society for Microbiology. All Rights Reserved.

This article is made available via the PMC Open Access Subset for unrestricted noncommercial re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

Keywords: SARS-CoV-2; COVID-19; Dogs; Cats; Wildlife.


Are #pangolins the intermediate #host of the 2019 novel #coronavirus (#SARS-CoV-2)? (PLOS Pathog., abstract)

[Source: PLOS Pathogens, full page: (LINK). Abstract, edited.]


Are pangolins the intermediate host of the 2019 novel coronavirus (SARS-CoV-2)?

Ping Liu , Jing-Zhe Jiang , Xiu-Feng Wan, Yan Hua, Linmiao Li, Jiabin Zhou, Xiaohu Wang, Fanghui Hou, Jing Chen, Jiejian Zou, Jinping Chen

Published: May 14, 2020 | DOI: https://doi.org/10.1371/journal.ppat.1008421



The outbreak of a novel corona Virus Disease 2019 (COVID-19) in the city of Wuhan, China has resulted in more than 1.7 million laboratory confirmed cases all over the world. Recent studies showed that SARS-CoV-2 was likely originated from bats, but its intermediate hosts are still largely unknown. In this study, we assembled the complete genome of a coronavirus identified in 3 sick Malayan pangolins. The molecular and phylogenetic analyses showed that this pangolin coronavirus (pangolin-CoV-2020) is genetically related to the SARS-CoV-2 as well as a group of bat coronaviruses but do not support the SARS-CoV-2 emerged directly from the pangolin-CoV-2020. Our study suggests that pangolins are natural hosts of Betacoronaviruses. Large surveillance of coronaviruses in pangolins could improve our understanding of the spectrum of coronaviruses in pangolins. In addition to conservation of wildlife, minimizing the exposures of humans to wildlife will be important to reduce the spillover risks of coronaviruses from wild animals to humans.


Author summary

Recently, a novel coronavirus, SARS-CoV-2, caused a still ongoing pandemic. Epidemiological study suggested this virus was associated with a wet market in Wuhan, China. However, the exact source of this virus is still unknown. In this study, we attempted to assemble the complete genome of a coronavirus identified from two groups of sick Malayan pangolins, which were likely to be smuggled for black market trade. The molecular and evolutionary analyses showed that this pangolin coronavirus we assembled was genetically associated with the SARS-CoV-2 but was not likely its precursor. This study suggested that pangolins are natural hosts of coronaviruses. Determining the spectrum of coronaviruses in pangolins can help understand the natural history of coronaviruses in wildlife and at the animal-human interface, and facilitate the prevention and control of coronavirus-associated emerging diseases.


Citation: Liu P, Jiang J-Z, Wan X-F, Hua Y, Li L, Zhou J, et al. (2020) Are pangolins the intermediate host of the 2019 novel coronavirus (SARS-CoV-2)? PLoS Pathog 16(5): e1008421. https://doi.org/10.1371/journal.ppat.1008421

Editor: Stanley Perlman, University of Iowa, UNITED STATES

Received: February 14, 2020; Accepted: April 8, 2020; Published: May 14, 2020

Copyright: © 2020 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All our files are available from the GeneBank database (accession number 2312773).

Funding: This project was supported by wildlife disease monitoring and early warning system maintenance project from National Forestry and Grassland Administration (2019072) to Chen JP, GDAS Special Project of Science and Technology Development (grant number 2020GDASYL-20200103090, 2018GDASCX-0107) to Liu P.,Guangzhou Science Technology and Innovation Commission (grant number 201804020080) to Chen JP, Natural Science Foundation of China (grant number 31972847) to Jiang JZ, Guangzhou science and technology project (grant number 2019001) to Chen JP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: No authors have competing interests.

Keywords: SARS-CoV-2; Betacoronavirus; Pangolins; Wildlife.


Multivariate #analyses of #codon usage of #SARS-CoV-2 and other #betacoronaviruses (Virus Evol., abstract)

[Source: Virus Evolution, full page: (LINK). Abstract, edited.]

Multivariate analyses of codon usage of SARS-CoV-2 and other betacoronaviruses

Haogao Gu, Daniel K W Chu, Malik Peiris, Leo L M Poon

Virus Evolution, Volume 6, Issue 1, January 2020,  veaa032, https://doi.org/10.1093/ve/veaa032

Published: 14 May 2020



Coronavirus disease 2019 (COVID-19) is a global health concern as it continues to spread within China and beyond. The causative agent of this disease, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belongs to the genus Betacoronavirus, which also includes severe acute respiratory syndrome-related coronavirus (SARSr-CoV) and Middle East respiratory syndrome-related coronavirus (MERSr-CoV). Codon usage of viral genes are believed to be subjected to different selection pressures in different host environments. Previous studies on codon usage of influenza A viruses helped identify viral host origins and evolution trends, however, similar studies on coronaviruses are lacking. In this study, we compared the codon usage bias using global correspondence analysis (CA), within-group CA and between-group CA. We found that the bat RaTG13 virus best matched the overall codon usage pattern of SARS-CoV-2 in orf1ab, spike and nucleocapsid genes, while the pangolin P1E virus had a more similar codon usage in membrane gene. The amino acid usage pattern of SARS-CoV-2 was generally found similar to bat and human SARSr-CoVs. However, we found greater synonymous codon usage differences between SARS-CoV-2 and its phylogenetic relatives on spike and membrane genes, suggesting these two genes of SARS-CoV-2 are subjected to different evolutionary pressures.

SARS-CoV-2, coronavirus, codon usage analysis, WCA


Keywords: SARS-CoV-2; COVID-19; Bats; Pangolins; Betacoronavirus.


A novel #bat #coronavirus closely related to #SARS-CoV-2 contains natural insertions at the #S1/S2 cleavage site of the #spike protein (Cell Curr Biol., abstract)

[Source: Cell Current Biology, full page: (LINK). Abstract, edited.]

A novel bat coronavirus closely related to SARS-CoV-2 contains natural insertions at the S1/S2 cleavage site of the spike protein

Hong Zhou 8, Xing Chen 8, Tao Hu 8, Juan Li 8, Hao Song, Yanran Liu, Peihan Wang, Di Liu, Jing Yang, Edward C. Holmes, Alice C. Hughes, Yuhai Bi, Weifeng Shi 9

Published: May 10, 2020 | DOI: https://doi.org/10.1016/j.cub.2020.05.023



The unprecedented pandemic of pneumonia caused by a novel coronavirus, SARS-CoV-2, in China and beyond has had major public health impacts on a global scale [1,2]. Although bats are regarded as the most likely natural hosts for SARS-CoV-2 [3], the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomics analysis of samples from 227 bats collected from Yunnan Province in China between May and October, 2019. Notably, RmYN02 shares 93.3% nucleotide identity with SARS-CoV-2 at the scale of the complete virus genome and 97.2% identity in the 1ab gene, in which it is the closest relative of SARS-CoV-2 reported to date. In contrast, RmYN02 showed low sequence identity (61.3%) to SARS-CoV-2 in the receptor binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, and in a similar manner to SARS-CoV-2, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the spike (S) protein. This provides strong evidence that such insertion events can occur naturally in animal betacoronaviruses.

Accepted: May 6, 2020 – Received in revised form: May 1, 2020 – Received: April 16, 2020

Publication stage In Press Accepted Manuscript

Identification DOI: https://doi.org/10.1016/j.cub.2020.05.023

Copyright © 2020 Elsevier Inc.

Keywords: Betacoronavirus; Bats; Wildlife; SARS-CoV-2.


#Isolation of #SARS-CoV-2-related #coronavirus from #Malayan #pangolins (Nature, abstract)

[Source: Nature, full page: (LINK). Abstract, edited.]

This is an unedited manuscript that has been accepted for publication. Nature Research are providing this early version of the manuscript as a service to our authors and readers. The manuscript will undergo copyediting, typesetting and a proof review before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins

Kangpeng Xiao, Junqiong Zhai, Yaoyu Feng, Niu Zhou, Xu Zhang, Jie-Jian Zou, Na Li, Yaqiong Guo, Xiaobing Li, Xuejuan Shen, Zhipeng Zhang, Fanfan Shu, Wanyi Huang, Yu Li, Ziding Zhang, Rui-Ai Chen, Ya-Jiang Wu, Shi-Ming Peng, Mian Huang, Wei-Jun Xie, Qin-Hui Cai, Fang-Hui Hou, Wu Chen, Lihua Xiao & Yongyi Shen

Nature (2020)



The outbreak of COVID-19 poses unprecedent challenges to global health1. The new coronavirus, SARS-CoV-2, shares high sequence identity to SARS-CoV and a bat coronavirus RaTG132. While bats may be the reservoir host for various coronaviruses3,4, whether SARS-CoV-2 has other hosts remains ambiguous. In this study, one coronavirus isolated from a Malayan pangolin showed 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S genes, respectively. In particular, the receptor-binding domain within the S protein of the Pangolin-CoV is virtually identical to that of SARS-CoV-2, with one noncritical amino acid difference. Results of comparative genomic analysis suggest that SARS-CoV-2 might have originated from the recombination of a Pangolin-CoV-like virus with a Bat-CoV-RaTG13-like virus. The Pangolin-CoV was detected in 17 of 25 Malayan pangolins analyzed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against Pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus that is highly related to SARS-CoV-2 in pangolins suggests that they have the potential to act as the intermediate host of SARS-CoV-2. The newly identified coronavirus in the most-trafficked mammal could represent a future threat to public health if wildlife trade is not effectively controlled.

Author notes: These authors contributed equally: Kangpeng Xiao, Junqiong Zhai

Keywords: SARS-CoV-2; COVID-19; Pangolins; Bats; Wildlife.


#SARS‐CoV‐2: #Spike glycoprotein structural #diversity, #phylogeny and potential #animal #host identification (J Med Virol., abstract)

[Source: Journal of Medical Virology, full page: (LINK). Abstract, edited.]

SARS‐CoV‐2: Spike glycoprotein structural diversity, phylogeny and potential animal host identification

Siarhei A. Dabravolski,  Yury K. Kavalionak

First published: 06 May 2020 | DOI:  https://doi.org/10.1002/jmv.25976

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jmv.25976



To investigate the evolutionary history of the current pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV2), a total of 137 genomes of coronavirus strains from elsewhere with release dates between January 2019 and 25 March 2020 were analysed. To investigate the potential intermediate host of the SARS‐CoV2, we have analysed spike glycoprotein sequences from different animals, with particular emphasize on bats. We performed phylogenetic analysis, structural reconstruction of the spike glycoproteins with subsequent alignment and comparison. Our phylogenetic results revealed that the SARS‐CoV2 was more similar to the bats’ betacoronavirus isolates: HKU5‐related from Pipistrellus abramus and HKU4‐related from Tylonycteris pachypus. We also identified a yak betacoronavirus strain YAK/HY24/CH/2017 as the closest match in the comparison of the spike glycoproteins structural models. Interestingly, a set of unique features described for this particular strain of the yak betacoronavirus. Therefore, our results suggest that the human SARS‐CoV2, responsible for the current outbreak of COVID‐19, could also come from the yak as an intermediate host.

This article is protected by copyright. All rights reserved.

Keywords: SARS-CoV-2; COVID-19; Betacoronavirus; Wildlife.


Commentary on: The #SARS, #MERS and novel #coronavirus (#COVID19) #epidemics, the newest and biggest #global #health #threats: what lessons have we learned? A #OneHealth approach to coronaviruses (Int J Epidemiol., summary)

[Source: International Journal of Epidemiology, full page: (LINK). Summary, edited.]

Commentary on: The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned? A One Health approach to coronaviruses

Laura H Kahn

International Journal of Epidemiology, dyaa071, https://doi.org/10.1093/ije/dyaa071

Published: 29 April 2020

Issue Section: Commentary


Peeri et al.1 have provided a comprehensive overview, comparing the epidemiological characteristics of and public health responses to three coronaviruses: Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and now SARS coronavirus 2 (SARS-CoV-2), which have emerged from animals into humans over the past 18 years. All three have been identified as betacoronaviruses. One Health is the concept that human, animal and environmental health are linked. It provides a useful framework for examining and dealing with emerging zoonotic diseases such as coronaviruses. In 2005, Lau et al.2 identified a coronavirus in non-caged Chinese horseshoe bats, which was closely related to the SARS-CoV isolated from civet cats and humans.


Keywords: SARS-CoV-2; COVID-19; Wildlife; Bats; Zoonoses; SARS; MERS-CoV.