Strategy To Assess Zoonotic Potential Reveals Low Risk Posed by SARS-Related Coronaviruses from Bat and Pangolin

Yang, Yong; Shen, Xu-Rui; Zhang, Yulan; Jiang, Ren-Di; Wang, Xi; Guan, Zhenqiong; Li, Qian; Yao, Yudong; Gong, Qian-Chun; Geng, Rong; Wang, Qi; Zhu, Yan; Luo, Jingyi; Z, Shi; Zhang, Huilan; Peng, Ke; Zhou, Peng

doi:10.1128/mbio.03285-22

Cited by 2 publications

(2 citation statements)

References 25 publications

(48 reference statements)

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“…52,53 Both WIV1 and RaTG13 originate from horseshoe bats, suggesting that the bat ACE2 receptor is lenient with respect to the fold of this loop, as at least two different conformations are permissive for bat ACE2 binding and cell entry, and three are permissive for human ACE2. 23,24,52,53,56 In the absence of a civet ACE2-bound spike structure, it is unknown if civet spikes are evolutionarily restricted by their corresponding civet ACE2 receptors from adopting a similar loop confirmation as that of SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 99%

Cryo-EM reveals variation in structural motifs within animal SARS-related coronavirus spike proteins

Bostina

Hills

Eruera

et al. 2023

Preprint

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SARS-CoV-2 is the third known coronavirus (CoV) that has crossed the animal-human barrier in the last two decades. However, little structural information exists related to the close genetic species within the SARS-related coronaviruses. Here, we present three novel SARS-related CoV spike protein structures solved by single particle cryo-electron microscopy analysis derived from bat (SL-CoV WIV1) and civet (CoV-SZ3, CoV-007) hosts. We report complex glycan trees that decorate the glycoproteins and density for water molecules which facilitated modeling of the water molecule coordination networks within structurally important regions. We note structural conservation of the fatty acid binding pocket and presence of a linoleic acid molecule, which are associated with stabilization of the receptor binding domains in the “down” conformation. Additionally, the N-terminal biliverdin binding pocket is occupied by a density in all the structures. Finally, we analyzed structural differences in a loop of the receptor binding motif between coronaviruses known to infect humans and the animal coronaviruses described in this study, which regulate binding to the human angiotensin converting enzyme 2 receptor. This study offers a structural framework to evaluate the origins of SARS-CoV-2, the risk of future cross-species transmission, the ability to inform pandemic prevention, and aid in the development of pan-neutralizing treatments.

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Section: Discussionmentioning

confidence: 99%

Cryo-EM reveals variation in structural motifs within animal SARS-related coronavirus spike proteins

Bostina

Hills

Eruera

et al. 2023

Preprint

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“…In vitro techniquesRecently, bat IFNs have been included in many in vitro studies. The majority of the research involved infecting bat cells with viruses (SARS-CoVs, Hendra and Marburg viruses) and measuring the induced expression level and antiviral response [107][108][109]. Various studies have compared the differences in antiviral IFN and IFNrelated gene responses between mammals and bats 110,111.…”

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confidence: 99%

Genomic and biological variation in bat IFNs: An antiviral treatment approach

AL‐Eitan,

Mihyar,

Zhang

et al. 2023

Reviews in Medical Virology

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Bat‐borne viruses have attracted considerable research, especially in relation to the Covid‐19 pandemic. Although bats can carry multiple zoonotic viruses that are lethal to many mammalian species, they appear to be asymptomatic to viral infection despite the high viral loads contained in their bodies. There are several differences between bats and other mammals. One of the major differences between bats and other mammals is the bats' ability to fly, which is believed to have induced evolutionary changes. It may have also favoured them as suitable hosts for viruses. This is related to their tolerance to viral infection. Innate immunity is the first line of defence against viral infection, but bats have metamorphosed the type of responses induced by innate immunity factors such as interferons. The expression patterns of interferons differ, as do those of interferon‐related genes such as interferon regulatory factors and interferon‐stimulated genes that contribute to the antiviral response of infected cells. In addition, the signalling pathways related to viral infection and immune responses have been subject to evolutionary changes, including mutations compared to their homologues in other mammals and gene selection. This article discusses the differences in the interferon‐mediated antiviral response in bats compared to that of other mammals and how these differences are correlated to viral tolerance in bats. The effect of bat interferons related genes on human antiviral response against bat‐borne viruses is also discussed.

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Strategy To Assess Zoonotic Potential Reveals Low Risk Posed by SARS-Related Coronaviruses from Bat and Pangolin

Abstract: Evaluation of the zoonotic risk of animal SARSr-CoVs is important for future disease preparedness. However, there are misconceptions regarding the risk of animal viruses.

Cited by 2 publications

References 25 publications

Cryo-EM reveals variation in structural motifs within animal SARS-related coronavirus spike proteins

Cryo-EM reveals variation in structural motifs within animal SARS-related coronavirus spike proteins

Genomic and biological variation in bat IFNs: An antiviral treatment approach

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