Determinants of supplier payment times before and during the pandemic: Empirical evidence from UK firms

Timely, compliant payment to suppliers is a significant issue in purchasing and supply management (PSM) but research into its determinants is limited. Here we draw on social responsibility, fintech and digital purchasing literatures, and institutional and stakeholder theories to explain variations in supplier payment times. A sample of 509 firms spanning 2018–2021 is used for panel regression analysis. Contrary to expectations, the COVID-19 pandemic did not lead to longer payment times or reduced compliance with payment terms, which we attribute to state-funded business supports and corporate decisions to accelerate payment to vulnerable suppliers. Institutional pressure in the form of payment codes was associated with shorter payment times and improved compliance during the pandemic. Supply chain finance (SCF) was associated with longer payment times during the pandemic while e-invoicing had no effect. Overall, institutional pressure seems to contribute to faster payment but stakeholder-centred fintech and digitalisation does not.

Modelling the pulse population-wide nucleic acid screening in mitigating and stopping COVID-19 outbreaks in China.

BACKGROUND: During 2021-2022, mainland China experienced multiple times of local COVID-19 outbreaks in several cities, including Yangzhou, Xi'an etc., and the Chinese government persistently adopted the zero-COVID policy in combating with the local outbreaks. METHODS: We develop a mathematical model with pulse population-wide nucleic acid screening, part of the zero-COVID policy, to reveal its role in controlling the spread of COVID-19. We calibrate the model by fitting the COVID-19 epidemic data of the local outbreaks in Yangzhou and Xi'an, China. Sensitivity analysis is conducted to investigate the impact of population-wide nucleic acid screening on controlling the outbreak of COVID-19. RESULTS: Without the screening, the cumulative number of confirmed cases increases by [Formula: see text] and [Formula: see text] in Yangzhou and Xi'an, respectively. Meanwhile, the screening program helps to shorten the lockdown period for more than one month when we aim at controlling the cases into zero. Considering its role in mitigating the epidemics, we observe a paradox phenomenon of the screening rate in avoiding the runs on medical resource. That is, the screening will aggravate the runs on medical resource when the screening rate is small, while it helps to relieve the runs on medical resource if the screening rate is high enough. We also conclude that the screening has limited effects on mitigating the epidemics if the outbreak is in a high epidemic level or there has already been runs on medical resources. Alternatively, a smaller screening population per time with a higher screening frequency may be a better program to avoid the runs on medical resources. CONCLUSIONS: The population-wide nucleic acid screening strategy plays an important role in quickly controlling and stopping the local outbreaks under the zero-COVID policy. However, it has limited impacts and even increase the potential risk of the runs on medical resource for containing the large scale outbreaks.

Robust therapeutic effects on COVID-19 of novel small molecules: Alleviation of SARS-CoV-2 S protein induction of ACE2/TMPRSS2, NOX2/ROS, and MCP-1.

While new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constantly emerge to prolong the pandemic of COVID-19, robust and safe therapeutics are in urgent need. During the previous and ongoing fight against the pandemic in China, Traditional Chinese Medicine (TCM) has proven to be markedly effective in treating COVID-19. Among active ingredients of TCM recipes, small molecules such as quercetin, glabridin, gallic acid, and chrysoeriol have been predicted to target viral receptor angiotensin-converting enzyme 2 (ACE2) via system pharmacology/molecular docking/visualization analyses. Of note, endothelial dysfunction induced by oxidative stress and inflammation represents a critical mediator of acute respiratory distress syndrome (ARDS) and multi-organ injuries in patients with COVID-19. Hence, in the present study, we examined whether quercetin, glabridin, gallic acide and chrysoeriol regulate viral receptors of ACE2 and transmembrane serine protease 2 (TMPRSS2), redox modulator NADPH oxidase isoform 2 (NOX2), and inflammatory protein of monocyte chemoattractant protein-1 (MCP-1) in endothelial cells to mediate therapeutic protection against COVID-19. Indeed, quercetin, glabridin, gallic acide and chrysoeriol completely attenuated SARS-CoV-2 spike protein (S protein)-induced upregulation in ACE2 protein expression in endothelial cells. In addition, these small molecules abolished S protein upregulation of cleaved/active form of TMPRSS2, while native TMPRSS2 was not significantly regulated. Moreover, these small molecules completely abrogated S protein-induced upregulation in NOX2 protein expression, which resulted in alleviated superoxide production, confirming their preventive efficacies against S protein-induced oxidative stress in endothelial cells. In addition, treatment with these small molecules abolished S protein induction of MCP-1 expression. Collectively, our findings for the first time demonstrate that these novel small molecules may be used as novel and robust therapeutic options for the treatment of patients with COVID-19, via effective attenuation of S protein induction of endothelial oxidative stress and inflammation.

Sparse and risk diversification portfolio selection.

Portfolio risk management has become more important since some unpredictable factors, such as the 2008 financial crisis and the recent COVID-19 crisis. Although the risk can be actively managed by risk diversification, the high transaction cost and managerial concerns ensue by over diversifying portfolio risk. In this paper, we jointly integrate risk diversification and sparse asset selection into mean-variance portfolio framework, and propose an optimal portfolio selection model labeled as JMV. The weighted piecewise quadratic approximation is considered as a penalty promoting sparsity for the asset selection. The variance associated with the marginal risk regard as another penalty term to diversify the risk. By exposing the feature of JMV, we prove that the KKT point of JMV is the local minimizer if the regularization parameter satisfies a mild condition. To solve this model, we introduce the accelerated proximal gradient (APG) algorithm [Wen in SIAM J. Optim 27:124-145, 2017], which is one of the most efficient first-order large-scale algorithm. Meanwhile, the APG algorithm is linearly convergent to a local minimizer of the JMV model. Furthermore, empirical analysis consistently demonstrate the theoretical results and the superiority of the JMV model.

The mechanism of Qingwen Gupi decoction on pulmonary fibrosis based on metabolomics and intestinal flora.

AIMS: To evaluate the effects of the Qingwen Gupi decoction (QGT) in a rat model of bleomycin-induced pulmonary fibrosis (PF), and explore the underlying mechanisms by integrating UPLC-Q-TOF/MS metabolomics and 16S rDNA sequencing of gut microbiota. METHODS AND RESULTS: The animals were randomly divided into the control, PF model, pirfenidone-treated, and low-, medium-, and high-dose QGT groups. The lung tissues were examined and the expression of TGF-ß, SMAD-3, and SMAD-7 mRNAs in the lung tissues were analyzed. Metabolomic profiles were analyzed by UPLC-QTOF/MS, and the intestinal flora were examined by prokaryotic 16 rDNA sequencing. Pathological examination and biochemical indices revealed that QGT treatment improved the symptoms of PF by varying degrees. Furthermore, QGT significantly downregulated TGF-ß1 and Smad-3 mRNAs and increased the expression levels of Smad-7. QGT-L in particular increased the levels of 18 key metabolic biomarkers that were associated with nine gut microbial species and may exert antifibrosis effects through arachidonic acid metabolism, glycerophospholipid metabolism, and phenylalanine metabolism. CONCLUSIONS: QGT alleviated PF in a rat model through its anti-inflammatory, antioxidant, and anti-fibrotic effects, and by reversing bleomycin-induced gut dysbiosis.This study lays the foundation for further research on the pathological mechanisms of PF and the development of new drug candidates.

SARS-CoV-2 impairs interferon production via NSP2-induced repression of mRNA translation.

Viruses evade the innate immune response by suppressing the production or activity of cytokines such as type I interferons (IFNs). Here we report the discovery of a mechanism by which the SARS-CoV-2 virus coopts an intrinsic cellular machinery to suppress the production of the key immunostimulatory cytokine IFN-ß. We reveal that the SARS-CoV-2 encoded nonstructural protein 2 (NSP2) directly interacts with the cellular GIGYF2 protein. This interaction enhances the binding of GIGYF2 to the mRNA cap-binding protein 4EHP, thereby repressing the translation of the Ifnb1 mRNA. Depletion of GIGYF2 or 4EHP significantly enhances IFN-ß production, which inhibits SARS-CoV-2 replication. Our findings reveal a target for rescuing the antiviral innate immune response to SARS-CoV-2 and other RNA viruses.

Case report: Anti-CNTN1 antibody-associated nodopathies disease with asymmetric onset.

Anti-contactin-1 (CNTN1) IgG4 antibody-associated nodopathies is an autoimmune antibody-mediated peripheral neuropathy with a unique clinical presentation, pathophysiology, electrophysiology, and therapeutic response. The critical histopathological features are a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. Here, a 62-year-old male patient presented with subacute unilateral limb onset, progressive exacerbation, marked weakness of the extremities, cranial, and autonomic nerve involvement. Neurophysiology showed slowed motor nerve conduction velocity (MCV), prolonged distal motor delay (DML), slowed sensory nerve conduction velocity (SCV), decreased sensory nerve activity potential (SNAP) amplitude, decreased amplitude of bilateral neuromotor conduction, abnormal cutaneous sympathetic response (SSR) in both lower extremities, axonal damage, prolonged F-wave latency, and discrete waves. In the initial phase, there was a response to intravenous immunoglobulin (IVIG), and corticosteroids and rituximab were also effective. After 1 year follow-up, the patient improved significantly. This article reports on a patient with nodular disease with anti-contactin-1 (CNTN1) IgG4 antibodies and reviews the literature to improve clinicians' understanding of the disease.

Identification of Potential Lead Compounds Targeting Novel Druggable Cavity of SARS-CoV-2 Spike Trimer by Molecular Dynamics Simulations.

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become an urgent public health problem. Spike (S) protein mediates the fusion between the virus and the host cell membranes, consequently emerging as an important target of drug design. The lack of comparisons of in situ full-length S homotrimer structures in different states hinders understanding the structures and revealing the function, thereby limiting the discovery and development of therapeutic agents. Here, the steady-state structures of the in situ full-length S trimer in closed and open states (Sclosed and Sopen) were modeled with the constraints of density maps, associated with the analysis of the dynamic structural differences. Subsequently, we identified various regions with structure and property differences as potential binding pockets for ligands that promote the formation of inactive trimeric protein complexes. By using virtual screening strategy and a newly defined druggable cavity, five ligands were screened with potential bioactivities. Then molecular dynamic (MD) simulations were performed on apo protein structures and ligand bound complexes to reveal the conformational changes upon ligand binding. Our simulation results revealed that sulforaphane (SFN), which has the best binding affinity, could inhibit the conformational changes of S homotrimer that would occur during the viral membrane fusion. Our results could aid in the understanding of the regulation mechanism of S trimer aggregation and the structure-activity relationship, facilitating the development of potential antiviral agents.

Age at SARS-CoV-2 infection and psychological and physical recovery among Chinese health care workers with severe COVID-19 at 28 months after discharge: A cohort study

Background No prior study had reported the psychological and physical recovery of patients with COVID-19 2~3 years after discharge from the hospital. Moreover, it is not clear whether there is any difference in the health status of the patients with COVID-19 of different ages after discharge from the hospital. Methods Embedding in the "Rehabilitation Care Project for Medical Staff Infected with COVID-19” in China, this study included 271 health care workers (HCWs) with severe COVID-19. Their status of health-related quality of life, persistent symptoms, functional fitness and immune function at 28 months after discharge were followed, and compared according to tertiles of age at SARS-CoV-2 infection (group of younger (≤ 33 years);medium (34-42 years);and older (≥43 years)). Multivariate linear regression and multivariable adjusted logistic regression models were applied in investigating the associations of age at SARS-CoV-2 infection and outcomes. Results At 28 months after discharge, 76% of the HCWs with severe COVID-19 had symptom of fatigue/weakness;18.7% of the HCWs with severe COVID-19 did not fully recover their functional fitness;the decrease of CD3+ T cells, CD8+ T cells and the increase of natural killer cells accounted for 6.6, 6.6, and 5.5%, respectively. Compared with the HCWs with severe COVID-19 in younger group, HCWs with severe COVID-19 in older group had lower scores regarding physical functioning, role physical, bodily pain and role emotional;HCWs with severe COVID-19 in older group had higher risk of cough, joint pain, hearing loss and sleep disorder;HCWs with severe COVID-19 in older group scored lower on flexibility test. The variance of relative numbers of CD3+ T cells, CD8+ T cells and natural killer cells among HCWs with severe COVID-19 of different age groups were significant. Conclusions This study demonstrated that older HCWs with severe COVID-19 recovered slower than those with younger age regarding health-related quality of life, persistent symptoms, functional fitness and immune function at 28 months after discharge. Effective exercise interventions regarding flexibility should be performed timely to speed their rehabilitation, especially among those with older age.

Insight into the mechanisms of coronaviruses evading host innate immunity

The SARS-CoV-2 induced coronavirus disease (COVID-19) has recently caused a pandemic. Patients with COVID-19 presented with a wide spectrum of symptoms for the disease, from entirely asymptomatic to full-blown pneumonia and multiorgan failures. More evidence emerged, showing the production of interferons (IFNs) in the severe cases were significantly lower than their milder counterparts, suggesting linkage of COVID-19 to impaired innate immunity. This review presents a brief overview of how coronaviruses evade innate immunity, based on the information from SARS-CoV and MERS-CoV. The coronaviruses manage to block, escape, or dampen the innate immune response by antagonizing double-stranded RNA (dsRNA) sensor, stimulator of IFN genes (STING) and mitochondrial antiviral-signaling protein (MAVS) pathways, epigenetic modification, posttranslational modifications, and host mRNA translation. We provide novel insights into a comprehensive therapy to combat SARS-CoV-2 infection.

A cross-sectional study on burnout and its individual and environmental correlates among hepatological surgery nurses in Hunan Province, China.

BACKGROUND: Burnout is a widespread occupational phenomenon among nurses with significant adverse outcomes for nurses, patients, and society. It is thus important and urgent to understand burnout and its risk factors to guide interventions. This study aimed to examine the level of burnout and explore its individual and environmental correlates. METHODS: This cross-sectional study was conducted in Hunan, China. A total of 623 hepatological surgery nurses completed an online survey (response rate: 72.78%). Burnout was measured using the standard Maslach Burnout Inventory (MBI). Information on individual factors and environmental factors was collected by self-designed questionnaires. RESULTS: The scores of emotional exhaustion, depersonalization, and personal achievement in nurse burnout were 30 (26-34), 11 (8-14), and 23 (20-26) respectively. The prevalence of high burnout ranged from 52.81% for emotional exhaustion to 90.37% for decreased personal achievement. The three dimensions of burnout shared common correlates such as self-rated physical health and working environment, while also having additional unique correlates such as overwork, satisfaction with income, and age. CONCLUSION: Hepatological surgery nurses in Hunan Province are suffering from high levels of burnout, which requires public attention and urgent interventions. Improvement of the physical health and working environment of nurses may be the most beneficial intervention measures to tackle various dimensions of burnout, while other targeted measures are also needed for each specific dimension.

Insight into the mechanisms of coronaviruses evading host innate immunity.

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) induced coronavirus disease 2019 (COVID-19) has recently caused a pandemic. Patients with COVID-19 presented with a wide spectrum of symptoms for the disease, from entirely asymptomatic disease to full-blown pneumonia and multiorgan failures. More evidence emerged, showing the production of interferons (IFNs) in the severe cases were significantly lower than their milder counterparts, suggesting linkage of COVID-19 to impaired innate immunity. This review presents a brief overview of how coronaviruses evade innate immunity, according to the current studies about SARS-CoV and middle-east respiratory syndrome-coronavirus (MERS-CoV). The coronaviruses manage to block, escape, or dampen the innate immune response by antagonizing double-stranded RNA (dsRNA) sensor, mitochondrial antiviral-signaling protein (MAVS) and stimulator of IFN genes (STING) pathways, epigenetic modification, posttranslational modifications, and host mRNA translation. We provide novel insights into a comprehensive therapy to combat SARS-CoV-2 infection.

Mental health, health-related quality of life, and lung function after hospital discharge in healthcare workers with severe COVID-19: a cohort study from China. / ä¸­å›½é‡ç—‡æ–°å† è‚ºç‚ŽåŒ»åŠ¡äººå‘˜å‡ºé™¢åŽå¿ƒç†å¥åº·ã€å¥åº·ç›¸å ³ç”Ÿæ´»è´¨é‡å’Œè‚ºåŠŸèƒ½éšè®¿è°ƒæŸ¥.

Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It is highly contagious and can cause death in severe cases. As reported by the World Health Organization (WHO), as of 6:36 pm Central European Summer Time (CEST), 12 August 2022, there had been 585 950 285 confirmed cases of COVID-19, including 6 425 422 deaths (WHO, 2022).

Age at SARS-CoV-2 infection and psychological and physical recovery among Chinese health care workers with severe COVID-19 at 28 months after discharge: A cohort study.

Background: No prior study had reported the psychological and physical recovery of patients with COVID-19 2~3 years after discharge from the hospital. Moreover, it is not clear whether there is any difference in the health status of the patients with COVID-19 of different ages after discharge from the hospital. Methods: Embedding in the "Rehabilitation Care Project for Medical Staff Infected with COVID-19" in China, this study included 271 health care workers (HCWs) with severe COVID-19. Their status of health-related quality of life, persistent symptoms, functional fitness and immune function at 28 months after discharge were followed, and compared according to tertiles of age at SARS-CoV-2 infection (group of younger (≤ 33 years); medium (34-42 years); and older (≥43 years)). Multivariate linear regression and multivariable adjusted logistic regression models were applied in investigating the associations of age at SARS-CoV-2 infection and outcomes. Results: At 28 months after discharge, 76% of the HCWs with severe COVID-19 had symptom of fatigue/weakness; 18.7% of the HCWs with severe COVID-19 did not fully recover their functional fitness; the decrease of CD3+ T cells, CD8+ T cells and the increase of natural killer cells accounted for 6.6, 6.6, and 5.5%, respectively. Compared with the HCWs with severe COVID-19 in younger group, HCWs with severe COVID-19 in older group had lower scores regarding physical functioning, role physical, bodily pain and role emotional; HCWs with severe COVID-19 in older group had higher risk of cough, joint pain, hearing loss and sleep disorder; HCWs with severe COVID-19 in older group scored lower on flexibility test. The variance of relative numbers of CD3+ T cells, CD8+ T cells and natural killer cells among HCWs with severe COVID-19 of different age groups were significant. Conclusions: This study demonstrated that older HCWs with severe COVID-19 recovered slower than those with younger age regarding health-related quality of life, persistent symptoms, functional fitness and immune function at 28 months after discharge. Effective exercise interventions regarding flexibility should be performed timely to speed their rehabilitation, especially among those with older age.

Cross-species transmission, evolution and zoonotic potential of coronaviruses.

Coronaviruses (CoVs) continuously evolve, crossing species barriers and spreading across host ranges. Over the last two decades, several CoVs (HCoV-229E, HCoV-NL63, HCoV-HKU1, HCoV-OC43, SARS-CoV, MERS-CoV, and SARS-CoV-2) have emerged in animals and mammals, causing significant economic and human life losses. Due to CoV cross-species transmission and the evolution of novel viruses, it is critical to identify their natural reservoiurs and the circumstances under which their transmission occurs. In this review, we use genetic and ecological data to disentangle the evolution of various CoVs in wildlife, humans, and domestic mammals. We thoroughly investigate several host species and outline the epidemiology of CoVs toward specific hosts. We also discuss the cross-species transmission of CoVs at the interface of wildlife, animals, and humans. Clarifying the epidemiology and diversity of species reservoirs will significantly impact our ability to respond to the future emergence of CoVs in humans and domestic animals.

A Dynamic Analysis of Conspiratorial Narratives on Twitter During the Pandemic.

Since the breakout of COVID-19 in late 2019, various conspiracy theories have spread widely on social media and other channels, fueling misinformation about the origins of COVID-19 and the motives of those working to combat it. This study analyzes tweets (N = 313,088) collected over a 9-month period in 2020, which mention a set of well-known conspiracy theories about the role of Bill Gates during the pandemic. Using a topic modeling technique (i.e., Biterm Topic Model), this study identified ten salient topics surrounding Bill Gates on Twitter, and we further investigated the interactions between different topics using Granger causality tests. The results demonstrate that emotionally charged conspiratorial narratives are more likely to breed other conspiratorial narratives in the following days. The findings show that each conspiracy theory is not isolated by itself. Instead, they are highly dynamic and interwoven. This study presents new empirical insights into how conspiracy theories spread and interact during crises. Practical and theoretical implications are also discussed.

Ocular Adverse Events after Inactivated COVID-19 Vaccination.

PURPOSE: To report the clinical characteristics of ocular adverse events that have occurred, in China, after vaccination with inactivated COVID-19 vaccines. METHODS: A retrospective cross-sectional observational study was conducted of ocular disorders that occurred within 15 days from any dose of an inactivated COVID-19 vaccine. Information on gender, age, the interval between the vaccination and ocular symptoms, laterality, duration of the ocular symptoms, primary visual acuity, and clinical diagnosis were retrospectively collected. RESULTS: Twenty-four patients were involved in the study, including 15 females and 9 males, with a mean age of 41 ± 16 years (range of 8-71 years). The patients all denied a prior history of COVID-19 infection. Ocular adverse events occurred after the first dose of vaccine in 18 patients and, after the second or third doses, in six patients. The interval between vaccination with the inactivated COVID-19 vaccine and ocular symptoms was 6 ± 5 days; six patients were bilaterally involved and 18 patients were unilaterally involved. Regarding the diagnosis, 10 patients were diagnosed with white dot syndrome (WDS), 9 patients were diagnosed with uveitis, and 5 patients were diagnosed with retinal vascular disorders. The ages of patients with WDS were younger than those with uveitis or retinal vascular disorders (32 ± 10 vs. 48 ± 18, p < 0.05). For patients diagnosed with WDS, the best-corrected visual acuity (BCVA) was 0.74 ± 0.73 LogMAR. For patients diagnosed with retinal vascular disorders or uveitis, the BCVA was 1.44 ± 1.26 LogMAR. There was no significant difference (p > 0.05). CONCLUSIONS: A relationship cannot be established between inactivated COVID-19 vaccines and ocular disorders; therefore, further investigation of the clinical spectrum of ocular adverse events after vaccination with an inactivated COVID-19 vaccine is necessary.

Mucociliary clearance augmenting drugs block SARS-CoV-2 replication in human airway epithelial cells.

The coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2 coronavirus, is devastatingly impacting human health. A prominent component of COVID-19 is the infection and destruction of the ciliated respiratory cells, which perpetuates dissemination and disrupts protective mucociliary transport (MCT) function, an innate defense of the respiratory tract. Thus, drugs that augment MCT could improve the barrier function of the airway epithelium and reduce viral replication and, ultimately, COVID-19 outcomes. We tested five agents known to increase MCT through distinct mechanisms for activity against SARS-CoV-2 infection using a model of human respiratory epithelial cells terminally differentiated in an air/liquid interphase. Three of the five mucoactive compounds tested showed significant inhibitory activity against SARS-CoV-2 replication. An archetype mucoactive agent, ARINA-1, blocked viral replication and therefore epithelial cell injury; thus, it was further studied using biochemical, genetic, and biophysical methods to ascertain the mechanism of action via the improvement of MCT. ARINA-1 antiviral activity was dependent on enhancing the MCT cellular response, since terminal differentiation, intact ciliary expression, and motion were required for ARINA-1-mediated anti-SARS-CoV2 protection. Ultimately, we showed that the improvement of cilia movement was caused by ARINA-1-mediated regulation of the redox state of the intracellular environment, which benefited MCT. Our study indicates that intact MCT reduces SARS-CoV-2 infection, and its pharmacologic activation may be effective as an anti-COVID-19 treatment.

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

In the last 2 decades, pathogens originating in animals may have triggered three coronavirus pandemics, including the coronavirus disease 2019 pandemic. Thus, evaluation of the spillover risk of animal severe acute respiratory syndrome (SARS)-related coronavirus (SARSr-CoV) is important in the context of future disease preparedness. However, there is no analytical framework to assess the spillover risk of SARSr-CoVs, which cannot be determined by sequence analysis alone. Here, we established an integrity framework to evaluate the spillover risk of an animal SARSr-CoV by testing how viruses break through key human immune barriers, including viral cell tropism, replication dynamics, interferon signaling, inflammation, and adaptive immune barriers, using human ex vivo lung tissues, human airway and nasal organoids, and human lung cells. Using this framework, we showed that the two pre-emergent animal SARSr-CoVs, bat BtCoV-WIV1 and pangolin PCoV-GX, shared similar cell tropism but exhibited less replicative fitness in the human nasal cavity or airway than did SARS-CoV-2. Furthermore, these viruses triggered fewer proinflammatory responses and less cell death, yet showed interferon antagonist activity and the ability to partially escape adaptive immune barriers to SARS-CoV-2. Collectively, these animal viruses did not fully adapt to spread or cause severe diseases, thus causing successful zoonoses in humans. We believe that this experimental framework provides a path to identifying animal coronaviruses with the potential to cause future zoonoses. IMPORTANCE 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. For example, an animal SARSr-CoV could readily infect humans. Alternately, human receptor usage may result in spillover risk. Here, we established an analytical framework to assess the zoonotic risk of SARSr-CoV by testing a series of virus-host interaction profiles. Our data showed that the pre-emergent bat BtCoV-WIV1 and pangolin PCoV-GX were less adapted to humans than SARS-CoV-2 was, suggesting that it may be extremely rare for animal SARSr-CoVs to break all bottlenecks and cause successful zoonoses.