Goh's BioComputing, Singapore 548957, Republic of Singapore.
Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.
J Proteome Res. 2020 Nov 6;19(11):4543-4552. doi: 10.1021/acs.jproteome.0c00460. Epub 2020 Aug 27.
A model to predict the relative levels of respiratory and fecal-oral transmission potentials of coronaviruses (CoVs) by measuring the percentage of protein intrinsic disorder (PID) of the M (Membrane) and N (Nucleoprotein) proteins in their outer and inner shells, respectively, was built before the MERS-CoV outbreak. With M = 8.6% and N = 50.2%, the 2003 SARS-CoV falls into group B, which consists of CoVs with intermediate levels of both fecal-oral and respiratory transmission potentials. Further validation of the model came with MERS-CoV (M = 9%, N = 44%) and SARS-CoV-2 (M = 5.5%, N = 48%) falling into the groups C and B, respectively. Group C contains CoVs with higher fecal-oral but lower respiratory transmission potentials. Unlike SARS-CoV, SARS-CoV-2 with M = 5.5% has one of the hardest outer shells among CoVs. Because the hard shell is able to resist the antimicrobial enzymes in body fluids, the infected person is able to shed large quantities of viral particles via saliva and mucus, which could account for the higher contagiousness of SARS-COV-2. Further searches have found that high rigidity of the outer shell is characteristic for the CoVs of burrowing animals, such as rabbits (M = 5.6%) and pangolins (M = 5-6%), which are in contact with the buried feces. A closer inspection of pangolin-CoVs from 2017 to 2019 reveals that pangolins provided a unique window of opportunity for the entry of an attenuated SARS-CoV-2 precursor into the human population in 2017 or earlier, with the subsequent slow and silent spread as a mild cold that followed by its mutations into the current more virulent form. Evidence of this lies in both the genetic proximity of the pangolin-CoVs to SARS-CoV-2 (∼90%) and differences in N disorder. A 2017 pangolin-CoV strain shows evidence of higher levels of attenuation and higher fecal-oral transmission associated with lower human infectivity via having lower N (44.8%). Our shell disorder model predicts this to be a SARS-CoV-2 vaccine strain, as lower inner shell disorder is associated with the lesser virulence in a variety of viruses.
在中东呼吸综合征冠状病毒（MERS-CoV）爆发之前，我们构建了一个模型，通过分别测量 M（膜）蛋白和 N（核蛋白）蛋白外、内层的蛋白无序性（PID）百分比，来预测冠状病毒呼吸传播和粪-口传播潜力的相对水平。2003 年的 SARS-CoV 的 M 值为 8.6%，N 值为 50.2%，属于 B 组，即具有中等粪-口和呼吸传播潜力的冠状病毒。对 MERS-CoV（M = 9%，N = 44%）和 SARS-CoV-2（M = 5.5%，N = 48%）的进一步验证结果分别落入 C 组和 B 组。C 组包含粪-口传播潜力较高但呼吸传播潜力较低的冠状病毒。与 SARS-CoV 不同，M 值为 5.5%的 SARS-CoV-2 是冠状病毒中外壳最硬的一种。由于硬壳能够抵抗体液中的抗菌酶，感染的人能够通过唾液和黏液大量排出病毒颗粒，这可能是 SARS-CoV-2 传染性更高的原因。进一步的搜索发现，外壳的高刚性是穴居动物冠状病毒的特征，例如兔子（M = 5.6%）和穿山甲（M = 5-6%），它们与埋藏的粪便接触。对 2017 年至 2019 年穿山甲冠状病毒的进一步检查表明，穿山甲为 2017 年或更早进入人类的 SARS-CoV-2 前体提供了一个独特的机会窗口，随后以温和感冒的形式缓慢而无声地传播，并在随后发生突变，形成目前更具毒性的形式。这一点的证据在于，穿山甲冠状病毒与 SARS-CoV-2 的遗传关系密切（~90%）和 N 无序性的差异。2017 年的穿山甲冠状病毒株显示出更高的衰减水平和更高的粪-口传播潜力，与较低的人类感染性相关，因为其 N 值较低（44.8%）。我们的外壳无序模型预测这将是一种 SARS-CoV-2 疫苗株，因为较低的内层无序性与各种病毒的较弱毒力相关。
