Cross-species tropism and antigenic landscapes of circulating SARS-CoV-2 variants

Zhang, Yali; Wei, Min; Wu, Yangtao; Wang, Juan; Hong, Yuting; Huang, Yang; Yuan, Lunzhi; Ma, Jian; Wang, Kai; Wang, Shaojuan; Shi, Yang; Wang, Zikang; Guo, Hao; Xiao, Jin; Yang, Changqing; Ye, Jianghui; Chen, Jijing; Liu, Yuxi; Fu, Baorong; Lan, Miaolin; Gong, Peixuan; Huang, Zehong; Su, Yingying; Chen, Yixin; Zhang, Tianying; Zhang, Jun; Zhu, Han; Yu, Hai; Yuan, Quan; Cheng, Tong; Guan, Yi; Xia, Ningshao

doi:10.1016/j.celrep.2022.110558

Cited by 30 publications

(24 citation statements)

References 35 publications

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“…Although some previously susceptible animal species seem to be resistant to variants such as Omicron BA.1 based on ACE2 binding data [19], the reverse trend wherein BA.1 appears to bind ACE2 from a broader range of species has also been observed [18]. One study suggests that multiple mutations to spike protein's receptor-binding domain may increase infectivity in sperm whales ( Physeter catodon ) [26]. Our work indicating that belugas and dolphins seem to be susceptible to Delta and Omicron variants of SARS-CoV-2 further challenges a scenario whereby SARS-CoV-2 is evolving to specialize solely on humans as hosts.…”

Section: Resultsmentioning

confidence: 99%

Beluga whale and bottlenose dolphin ACE2 proteins allow cell entry mediated by spike protein from three variants of SARS-CoV-2

Stone,

Unal,

Romano

et al. 2023

Biol. Lett.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses infect numerous non-human species. Spillover of SARS-CoV-2 into novel animal reservoirs may present a danger to host individuals of these species, particularly worrisome in populations already endangered or threatened by extinction. In addition, emergence in new reservoirs could pose spillback threats to humans, especially in the form of virus variants that further mutate when infecting other animal hosts. Previous work suggests beluga whales ( Delphinapterus leucas ) and bottlenose dolphins ( Tursiops truncatus ) may be at risk owing to their formation of social groups, contact with humans, exposure to contaminated wastewater, and structure of their angiotensin-converting enzyme 2 (ACE2) proteins, which SARS-CoV-2 uses as a cellular receptor. We examined marine-mammal susceptibility to virus infection by challenging 293T cells expressing beluga or dolphin ACE2 with pseudovirions bearing the SARS-CoV-2 spike protein. Beluga and dolphin ACE2 were sufficient to allow cell entry by an early pandemic isolate (Wuhan-Hu-1) and two evolved variants (Delta B.1.617.2 and Omicron BA.1 strains). We conclude that SARS-CoV-2 poses a potential threat to marine mammal reservoirs that should be considered in surveillance efforts.

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Section: Resultsmentioning

confidence: 99%

Beluga whale and bottlenose dolphin ACE2 proteins allow cell entry mediated by spike protein from three variants of SARS-CoV-2

Stone,

Unal,

Romano

et al. 2023

Biol. Lett.

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“…They also illustrated cross-species tropism in cells expressing 18 ACE2 molecules. This study may help to forecast the spread of mutations [ 61 ].…”

Section: Resultsmentioning

confidence: 99%

“…Zhang et al illustrated mutations in 11 VOCs and VOIs, including Omicron, and their effect on the nAb binding site. They concluded from their study that mutations near AA 439–448 and AA484 might cause resistance to neutralization [ 61 ]. Cui et al performed an experimental study and developed the Omicron pseudo-virus, attempted to correlate immunogenic areas with high mutation frequencies, and correlated them with properties such as immune escape and infectivity.…”

Section: Resultsmentioning

confidence: 99%

A comprehensive analysis of the mutational landscape of the newly emerging Omicron (B.1.1.529) variant and comparison of mutations with VOCs and VOIs

et al. 2022

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The Omicron variant is spreading rapidly throughout several countries. Thus, we comprehensively analyzed Omicron’s mutational landscape and compared mutations with VOC/VOI. We analyzed SNVs throughout the genome, and AA variants (NSP and SP) in VOC/VOI, including Omicron. We generated heat maps to illustrate the AA variants with high mutation prevalence (> 75% frequency) of Omicron, which demonstrated eight mutations with > 90% prevalence in ORF1a and 29 mutations with > 75% prevalence in S-glycoprotein. A scatter plot for Omicron and VOC/VOI’s cluster evaluation was computed. We performed a risk analysis of the antibody-binding risk among four mutations (L452, F490, P681, D614) and observed three mutations (L452R, F490S, D614G) destabilized antibody interactions. Our comparative study evaluated the properties of 28 emerging mutations of the S-glycoprotein of Omicron, and the ΔΔG values. Our results showed K417N with minimum and Q954H with maximum ΔΔG value. Furthermore, six important RBD mutations (G339D, S371L, N440K, G446S, T478K, Q498R) were chosen for comprehensive analysis for stabilizing/destabilizing properties and molecular flexibility. The G339D, S371L, N440K, and T478K were noted as stable mutations with 0.019 kcal/mol, 0.127 kcal/mol, 0.064 kcal/mol, and 1.009 kcal/mol. While, G446S and Q498R mutations showed destabilizing results. Simultaneously, among six RBD mutations, G339D, G446S, and Q498R mutations increased the molecular flexibility of S-glycoprotein. This study depicts the comparative mutational pattern of Omicron and other VOC/VOI, which will help researchers to design and deploy novel vaccines and therapeutic antibodies to fight against VOC/VOI, including Omicron. Supplementary Information The online version contains supplementary material available at 10.1007/s11357-022-00631-2.

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“…Receptor recognition is a primary barrier to cross-species transmission of coronaviruses, while adaptive antigenic drift could break this barrier and lead to spillover in other species 30 . Here we show that the T510F mutation in the NeoCoV spike, increasing binding affinity via interacting with a conserved hydrophobic pocket, broadens the potential host range.…”

Section: Discussionmentioning

confidence: 99%

Broad host tropism of ACE2-using MERS-related coronaviruses and determinants restricting viral recognition

Xiong

et al. 2022

Preprint

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Phylogenetically distant coronaviruses have evolved to employ ACE2 as their common receptors, including NL63 and many Severe acute respiratory syndrome (SARS) coronavirus-related viruses. Recently, we found two Middle East respiratory syndrome coronaviruses (MERS-CoV)-related bat coronaviruses, NeoCoV and PDF-2180, also use Angiotensin-converting enzyme 2(ACE2) but not MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) for entry. Receptor binding domain (RBD)-binding and pseudovirus entry assays based on a wide range of bat ACE2 orthologs revealed that the two viruses strongly prefer ACE2 from Yangochiropteran bats as compared with Yinpterochiropteran bats, which is not observed in NL63 and SARS-CoV-2. Genetic and structural analyses of the virus-receptor interactions of 50 bat ACE2 orthologs pointed to four crucial host range determinants in two viral binding loops on ACE2. Subsequent functional verifications via mutagenesis on representative ACE2 orthologs confirmed the importance of these determinants on human and bat cells. Remarkably, NeoCoV-T510F, a mutation previously shown to acquire human ACE2 recognition, displayed an expanded potential host range covering most tested bat ACE2, probably due to its reinforced interaction with an evolutionary conserved hydrophobic pocket. Our results elucidated the molecular mechanisms for the species-specific ACE2 usage of MERS-related viruses, offering basic information for assessing the zoonotic risk of these ACE2 utilizing merbecoviruses.

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Cross-species tropism and antigenic landscapes of circulating SARS-CoV-2 variants

Cited by 30 publications

References 35 publications

Beluga whale and bottlenose dolphin ACE2 proteins allow cell entry mediated by spike protein from three variants of SARS-CoV-2

Beluga whale and bottlenose dolphin ACE2 proteins allow cell entry mediated by spike protein from three variants of SARS-CoV-2

A comprehensive analysis of the mutational landscape of the newly emerging Omicron (B.1.1.529) variant and comparison of mutations with VOCs and VOIs

Broad host tropism of ACE2-using MERS-related coronaviruses and determinants restricting viral recognition

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