Broader-species receptor binding and structural bases of Omicron SARS-CoV-2 to both mouse and palm-civet ACE2s

Fu, Pingqing; Han, Pu; Huang, Baihan; Xie, Yufeng; Li, Weiwei; Zhang, Di; Han, Pengcheng; Xu, Zepeng; Bai, Bo; Zhou, Jingya; Kang, Xinrui; Li, Xiaomei; Zheng, Anqi; Zhang, Rong; Qiao, Shitong; Zhao, Xin; Qi, Jianxun; Wang, Qihui; Liu, Kefang; Gao, Lidong

doi:10.1038/s41421-022-00431-0

Cited by 35 publications

(28 citation statements)

References 67 publications

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“…In our study, the one-RBD-up conformation predominates in the apo, ACE2-, or S309-bound spike trimers. Furthermore, our group resolved the cryo-EM structure of the mouse ACE2-bound Omicron spike, which also adopts the one-RBD-up conformation 49 . These results indicate that the conformational changes from the down-RBD to the up-RBD of Omicron may be reduced, even adding the ACE2 receptor.…”

Section: Discussionmentioning

confidence: 99%

Omicron SARS-CoV-2 mutations stabilize spike up-RBD conformation and lead to a non-RBM-binding monoclonal antibody escape

et al. 2022

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Omicron SARS-CoV-2 is rapidly spreading worldwide. To delineate the impact of emerging mutations on spike’s properties, we performed systematic structural analyses on apo Omicron spike and its complexes with human ACE2 or S309 neutralizing antibody (NAb) by cryo-EM. The Omicron spike preferentially adopts the one-RBD-up conformation both before and after ACE2 binding, which is in sharp contrast to the orchestrated conformational changes to create more up-RBDs upon ACE2 binding as observed in the prototype and other four variants of concern (VOCs). Furthermore, we found that S371L, S373P and S375F substitutions enhance the stability of the one-RBD-up conformation to prevent exposing more up-RBDs triggered by ACE2 binding. The increased stability of the one-RBD-up conformation restricts the accessibility of S304 NAb, which targets a cryptic epitope in the closed conformation, thus facilitating the immune evasion by Omicron. These results expand our understanding of Omicron spike’s conformation, receptor binding and antibody evasion mechanism.

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Section: Discussionmentioning

confidence: 99%

Omicron SARS-CoV-2 mutations stabilize spike up-RBD conformation and lead to a non-RBM-binding monoclonal antibody escape

et al. 2022

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“…Moreover, the circulating variants such as Omicron and the emergence of new ones raise concerns regarding the risk of new mutations in SARS-CoV-2 that could expand host range susceptibility and generate new zoonotic reservoirs. In fact, a recent study with 27 ACE2 orthologues including goat suggests a broader species receptor binding of Omicron compared to other variants such as Delta [48]. Thus, the infectivity of new viral variants in different animal species should be continuously monitored as improved viral replication cannot be ruled out in species currently defined as poorly susceptible.…”

Section: Discussionmentioning

confidence: 99%

Susceptibility of Domestic Goat (Capra aegagrus hircus) to Experimental Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.351/Beta Variant

Fernández‐Bastit

Roca

Romero‐Durana

et al. 2022

Viruses

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A wide range of animal species are susceptible to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Natural and/or experimental infections have been reported in pet, zoo, farmed and wild animals. Interestingly, some SARS-CoV-2 variants, such as B.1.1.7/Alpha, B.1.351/Beta, and B.1.1.529/Omicron, were demonstrated to infect some animal species not susceptible to classical viral variants. The present study aimed to elucidate if goats (Capra aegagrus hircus) are susceptible to the B.1.351/Beta variant. First, an in silico approach was used to predict the affinity between the receptor-binding domain of the spike protein of SARS-CoV-2 B.1.351/Beta variant and angiotensin-converting enzyme 2 from goats. Moreover, we performed an experimental inoculation with this variant in domestic goat and showed evidence of infection. SARS-CoV-2 was detected in nasal swabs and tissues by RT-qPCR and/or immunohistochemistry, and seroneutralisation was confirmed via ELISA and live virus neutralisation assays. However, the viral amount and tissue distribution suggest a low susceptibility of goats to the B.1.351/Beta variant. Therefore, although monitoring livestock is advisable, it is unlikely that goats play a role as SARS-CoV-2 reservoir species, and they are not useful surrogates to study SARS-CoV-2 infection in farmed animals.

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“…Figure 5). For example, BA.1 S is known to interact differently with its cellular receptor ACE2, to utilise ACE2 from a broader range of species as receptor, and to mediate increased virus uptake [Cameroni et al, 2022; Hong et al, 2022; Li et al, 2022; Meng et al, 2022; Rathnasinge et al, 2022; Willett et al, 2022; Zhang et al, 2022].…”

Section: Discussionmentioning

confidence: 99%

Omicron-induced interferon signalling prevents influenza A virus infection

Bojkova

Bechtel

Rothenburger

et al. 2022

Preprint

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Recent findings in permanent cell lines suggested that SARS-CoV-2 Omicron BA.1 induces a stronger interferon response than Delta. Here, we show that BA.1 and BA.5 but not Delta induce an antiviral state in air-liquid interface (ALI) cultures of primary human bronchial epithelial (HBE) cells and primary human monocytes. Both Omicron subvariants caused the production of biologically active type I (alpha/beta) and III (lambda) interferons and protected cells from super-infection with influenza A viruses. Notably, abortive Omicron infection of monocytes was sufficient to protect monocytes from influenza A virus infection. Interestingly, while influenza-like illnesses surged during the Delta wave in England, their spread rapidly declined upon the emergence of Omicron. Mechanistically, Omicron-induced interferon signalling was mediated via double-stranded RNA recognition by MDA5, as MDA5 knock-out prevented it. The JAK/ STAT inhibitor baricitinib inhibited the Omicron-mediated antiviral response, suggesting it is caused by MDA5-mediated interferon production, which activates interferon receptors that then trigger JAK/ STAT signalling. In conclusion, our study 1) demonstrates that only Omicron but not Delta induces a substantial interferon response in physiologically relevant models, 2) shows that Omicron infection protects cells from influenza A virus super-infection, and 3) indicates that BA.1 and BA.5 induce comparable antiviral states.

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Broader-species receptor binding and structural bases of Omicron SARS-CoV-2 to both mouse and palm-civet ACE2s

Cited by 35 publications

References 67 publications

Omicron SARS-CoV-2 mutations stabilize spike up-RBD conformation and lead to a non-RBM-binding monoclonal antibody escape

Omicron SARS-CoV-2 mutations stabilize spike up-RBD conformation and lead to a non-RBM-binding monoclonal antibody escape

Susceptibility of Domestic Goat (Capra aegagrus hircus) to Experimental Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.351/Beta Variant

Omicron-induced interferon signalling prevents influenza A virus infection

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