Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Middle East respiratory syndrome coronavirus (MERS-CoV) infect the human respiratory tract. A prototype thermodynamic equilibrium model is presented here for the probability of the virions getting through the mucus barrier and infecting epithelial cells based on the binding affinity (K_mucin) of the virions to mucin molecules in the mucus and parameters for binding and infection of the epithelial cell. Both MERS-CoV and SARS-CoV-2 bind strongly to their cellular receptors, DDP4 and ACE2, respectively, and infect very efficiently both bronchus and lung ex vivo cell cultures which are not protected by a mucus barrier. According to the model, mucin binding could reduce the infectivity for MERS-CoV compared to SARS-CoV-2 by at least 100-fold depending on the magnitude of K_mucin. Specifically K_mucin values up to 10⁶ M⁻¹ have little protective effect and thus the mucus barrier would not remove SARS-CoV-2 which does not bind to sialic acids (SA) and hence would have a very low K_mucin. Depending on the viability of individual virions, the ID₅₀ for SARS-CoV-2 is estimated to be ~500 virions (viral RNA genomic copies) representing 1 to 2 pfu. In contrast MERS-CoV binds both SA and human mucin and a K_mucin of 5 × 10⁹ M⁻¹ as reported for lectins would mop up 99.83% of the virus according to the model with the ID₅₀ for MERS-CoV estimated to be ~295,000 virions (viral RNA genomic copies) representing 819 pfu. This could in part explain why MERS-CoV is poorly transmitted from human to human compared to SARS-CoV-2. Some coronaviruses use an esterase to escape the mucin, although MERS-CoV does not. Instead, it is shown here that “clustering” of virions into single aerosol particles as recently reported for rotavirus in extracellular vesicles could provide a co-operative mechanism whereby MERS-CoV could theoretically overcome the mucin barrier locally and a small proportion of 10 μm diameter aerosol particles could contain ~70 virions based on reported maximum levels in saliva. Although recent evidence suggests SARS-CoV-2 initiates infection in the nasal epithelium, the thermodynamic equilibrium models presented here could complement published approaches for modelling the physical entry of pathogens to the lung based on the fate and transport of the pathogen particles (as for anthrax spores) to develop a dose-response model for aerosol exposure to respiratory viruses. This would enable the infectivity through aerosols to be defined based on molecular parameters as well as physical parameters. The role of the spike proteins of MERS-CoV and SARS-CoV-2 binding to SA and heparan sulphate, respectively, may be to aid non-specific attachment to the host cell. It is proposed that a high K_mucin is the cost for subsequent binding of MERS-CoV to SAs on the cell surface to partially overcome the unfavourable entropy of immobilisation as the virus adopts the correct orientation for spike protein interactions with its protein cellular receptor DPP4.

严重的急性呼吸综合症冠状病毒2（SARS-CoV-2）和中东呼吸综合症冠状病毒（MERS-CoV）感染人的呼吸道。这里展示了一个原型热力学平衡模型，用于基于结合亲和力（K_粘蛋白）的病毒粒子穿过粘液屏障并感染上皮细胞的可能性。病毒颗粒与粘液中粘蛋白分子的结合以及上皮细胞结合和感染的参数。MERS-CoV和SARS-CoV-2都分别与它们的细胞受体DDP4和ACE2牢固结合，并非常有效地感染不受粘液屏障保护的支气管和肺离体细胞培养物。根据该模型，粘蛋白结合可以比SARS-CoV-2减少对MERS-CoV的感染性，这取决于K_粘蛋白的量，至少100倍。特别地，高达10 ⁶ M ^-1的K_粘蛋白几乎没有保护作用，因此粘液屏障不会去除不与唾液酸（SA）结合的SARS-CoV-2，因此K_粘蛋白非常低。根据各个病毒体的生存力，SARS-CoV-2的ID ₅₀估计为约500病毒体（病毒RNA基因组拷贝），代表1-2 pfu。相反，根据ID ₅₀的模型，MERS-CoV可以同时结合SA和人类黏_蛋白，据凝集素报道，K_黏蛋白为5×10 ⁹ M ^-1会清除99.83％的病毒。MERS-CoV的病毒估计为约295,000病毒体（病毒RNA基因组拷贝），代表819 pfu。这部分可以解释为什么相比于SARS-CoV-2，MERS-CoV在人与人之间的传播较差。一些冠状病毒使用酯酶逃避粘蛋白，尽管MERS-CoV却没有。取而代之的是，这里显示的是，最近报道的轮状病毒在细胞外小泡中将病毒粒子“聚类”为单个气溶胶颗粒可以提供一种合作机制，从而使MERS-CoV在理论上可以局部克服粘蛋白屏障，并且小部分直径为10μm根据报告的最高唾液水平，气溶胶颗粒可能含有约70个毒粒。尽管最近的证据表明SARS-CoV-2在鼻上皮细胞中引发感染，此处介绍的热力学平衡模型可以补充已发布的方法，用于根据病原体颗粒的命运和运输（如炭疽孢子）来模拟病原体向肺部的物理进入，从而开发出剂量-响应模型，以使气溶胶暴露于呼吸道病毒。这将使得可以基于分子参数以及物理参数定义通过气溶胶的传染性。MERS-CoV和SARS-CoV-2的刺突蛋白分别与SA和硫酸乙酰肝素结合的作用可能是帮助非特异性附着于宿主细胞。建议高K 这将使得可以基于分子参数以及物理参数定义通过气溶胶的传染性。MERS-CoV和SARS-CoV-2的刺突蛋白分别与SA和硫酸乙酰肝素结合的作用可能是帮助非特异性附着于宿主细胞。建议高K 这将使得可以基于分子参数以及物理参数定义通过气溶胶的传染性。MERS-CoV和SARS-CoV-2的刺突蛋白分别与SA和硫酸乙酰肝素结合的作用可能是帮助非特异性附着于宿主细胞。建议高K_粘蛋白是随后将MERS-CoV与细胞表面SA结合以部分克服固定化熵的代价，因为该病毒采用正确的方向进行刺突蛋白与其蛋白细胞受体DPP4的相互作用。