Insights into the cross-species evolution of 2019 novel coronavirus

Zhang, Jiahao; Jia, Weixin; Zhu, Junhai; Li, Bo; Xing, Jinchao; Liao, Ming; Qi, Wenbao

doi:10.1016/j.jinf.2020.02.025

Cited by 14 publications

(14 citation statements)

References 6 publications

(4 reference statements)

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“…The early daily reproduction number (R t ) of COVID-19 in Wuhan declined from 2.35 (95% CI, 1.15-4.77) [23]. It is still an emerging, rapidly evolving situation [24][25][26][27][28].…”

Section: Discussionmentioning

confidence: 99%

A cohort study of 676 patients indicates D-dimer is a critical risk factor for the mortality of COVID-19

Huang

Lyu

et al. 2020

PLoS ONE

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Coronavirus Disease 2019 (COVID-19) has recently become a public emergency and a worldwide pandemic. However, the information on the risk factors associated with the mortality of COVID-19 and of their prognostic potential is limited. In this retrospective study, the clinical characteristics, treatment and outcome data were collected and analyzed from 676 COVID-19 patients stratified into 140 non-survivors and 536 survivors. We found that the levels of Dimerized plasmin fragment D (D-dimer), C-reactive protein (CRP), lactate dehydrogenase (LDH), procalcitonin (PCT) were significantly higher in non-survivals on admission (non-survivors vs. survivors: D-Dimer ≥ 0.5 mg/L, 83.2% vs. 44.9%, P<0.01; CRP ≥10 mg/L, 50.4% vs. 6.0%, P<0.01; LDH ≥ 250 U/L, 73.8% vs. 20.1%, P<0.01; PCT ≥ 0.5 ng/ml, 27.7% vs. 1.8%, P<0.01). Moreover, dynamic tracking showed D-dimer kept increasing in non-survivors, while CRP, LDH and PCT remained relatively stable after admission. D-dimer has the highest C-index to predict in-hospital mortality, and patients with D-dimer levels ≥0.5 mg/L had a higher incidence of mortality (Hazard Ratio: 4.39, P<0.01). Our study suggested D-dimer could be a potent marker to predict the mortality of COVID-19, which may be helpful for the management of patients.

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“…The early daily reproduction number (R t ) of COVID-19 in Wuhan declined from 2.35 (95% CI, 1.15-4.77) [23]. It is still an emerging, rapidly evolving situation [24][25][26][27][28].…”

Section: Discussionmentioning

confidence: 99%

A cohort study of 676 patients indicates D-dimer is a critical risk factor for the mortality of COVID-19

Huang

Lyu

et al. 2020

PLoS ONE

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“…A newly reported bat RmYN02 shares 93.3% nucleotide identity with SARS-CoV-2 genomewide and 97.2% identity in the 1ab gene (2). Besides bat CoVs, pangolin/GD/2019 CoV and pangolin/GX/P5L/2017 CoV share up to 90% and 85.2% sequence identity with SARS-CoV-2, respectively (4,5). While the origin of SARS-CoV-2 appears to be linked to bat reservoirs, there is still no definitive evidence of an intermediate host that could have transmitted the virus to humans.…”

Section: Introductionmentioning

confidence: 97%

The PRRA Insert at the S1/S2 Site Modulates Cellular Tropism of SARS-CoV-2 and ACE2 Usage by the Closely Related Bat RaTG13

Selvaraj

Lien

et al. 2021

J Virol

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Biochemical and structural analyses suggest that SARS-CoV-2 is well-adapted to infecting humans and the presence of four residues (PRRA) at the S1/S2 site within the spike (S) protein, which may lead to unexpected tissue or host tropism. Here we report that SARS-CoV-2 efficiently utilized ACE2 of 9 species to infect 293T cells. Similarly, pseudoviruses bearing S protein derived from either the bat RaTG13 or pangolin GX, two closely related animal coronaviruses, utilized ACE2 of a diverse range of animal species to gain entry. Removal of PRRA from SARS-CoV-2 S protein displayed distinct effects on pseudoviral entry into different cell types. Unexpectedly, insertion of PRRA into the RaTG13 S protein selectively abrogated the usage of horseshoe bat and pangolin ACE2 but enhanced the usage of mouse ACE2 by the relevant pseudovirus to enter cells. Together, our findings identified a previously unrecognized effect of the PRRA insert on SARS-CoV-2 and RaTG13 S proteins. Importance The four-residue insert (PRRA) at the boundary between the S1and S2 subunits of SARS-CoV-2 has been widely recognized since day 1 for its role in SARS-CoV-2 S protein processing and activation. As this PRRA insert is unique to SARS-CoV-2 among group b betacoronaviruses, it is thought to affect the tissue and species tropism of SARS-CoV-2. We compared the usage of 10 ACE2 orthologs and found that the presence of PRRA not only affects the cellular tropism of SARS-CoV-2 but also modulates the usage of ACE2 orthologs by the closely related bat RaTG13 S protein. The binding of pseudovirions carrying RaTG13 S with a PRRA insert to mouse ACE2 was nearly 2-fold higher than that of pseudovirions carrying RaTG13 S.

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“…A newly reported bat RmYN02 shares 93.3% nucleotide identity with SARS-CoV-2 genomewide and 97.2% identity in the 1ab gene (Zhou et al, 2020a). Besides bat CoVs, pangolin/GD/2019 CoV and pangolin/GX/P5L/2017 CoV share up to 90% and 85.2% sequence identity with SARS-CoV-2, respectively (Liu et al, 2020;Zhang et al, 2020). While the origin of the novel coronavirus appears to be in bat reservoirs, there is still no definitive evidence of an intermediate host that could have transmitted the virus to humans.…”

Section: Introductionmentioning

confidence: 97%

The PRRA insert at the S1/S2 site modulates cellular tropism of SARS-CoV-2 and ACE2 usage by the closely related Bat raTG13

Selvaraj

Lien

et al. 2020

Preprint

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SummaryBiochemical and structural analyses suggest that SARS-CoV-2 is well-adapted to infecting human and the presence of four residues (PRRA) at the S1/S2 site within the Spike protein may lead to unexpected tissue or host tropism. Here we report that SARS-CoV-2 efficiently utilized ACE2 of 9 species except mouse to infect 293T cells. Similarly, pseudoviruses bearing spike protein derived from either the bat raTG13 or pangolin GX, two closely related animal coronaviruses, utilized ACE2 of a diverse range of animal species to gain entry. Removal of PRRA from SARS-CoV-2 Spike displayed distinct effects on pseudoviral entry into different cell types. Strikingly, insertion of PRRA into the raTG13 Spike selectively abrogated the usage of horseshoe bat and pangolin ACE2 but conferred usage of mouse ACE2 by the relevant pseudovirus to enter cells. Together, our findings identified a previously unrecognized effect of the PRRA insert on SARS-CoV-2 and raTG13 spike proteins.

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Insights into the cross-species evolution of 2019 novel coronavirus

Cited by 14 publications

References 6 publications

A cohort study of 676 patients indicates D-dimer is a critical risk factor for the mortality of COVID-19

A cohort study of 676 patients indicates D-dimer is a critical risk factor for the mortality of COVID-19

The PRRA Insert at the S1/S2 Site Modulates Cellular Tropism of SARS-CoV-2 and ACE2 Usage by the Closely Related Bat RaTG13

The PRRA insert at the S1/S2 site modulates cellular tropism of SARS-CoV-2 and ACE2 usage by the closely related Bat raTG13

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