Abstract
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 MPID = 8.6% and NPID = 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 (MPID = 9%, NPID = 44%) and SARS-CoV-2 (MPID = 5.5%, NPID = 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 MPID = 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 (MPID = 5.6%) and pangolins (MPID = 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 NPID (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.
Highlights
COVID-19 and SARS-COV-2In December 2019, physicians in Wuhan, China, began to notice a large number of patients with a severe pneumonia-like illness that did not respond to antibiotics
Article can be found among animals such as horseshoe bats and civet cats,[2,3] close relatives of SARS-CoV-2 were found in bats (RATG13) and pangolins.[4,5,7,10−12] In line with the debates on the actual identity of the animal intermediary of SARS-CoV2,8,9,11,12 are we presenting here more evidence of the greater likelihood that pangolins served as an intermediary host, but we are able to detect the existence of attenuated strains of CoV closely related to SARS-CoV-2
The model measured the level of intrinsic disorder in proteins comprising the outer and inner shells of CoVs, M and N
Summary
COVID-19 and SARS-COV-2In December 2019, physicians in Wuhan, China, began to notice a large number of patients with a severe pneumonia-like illness that did not respond to antibiotics. A novel coronavirus that is closely related to the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV) was quickly identified to be responsible for the illness. The model predicted that SARS-CoV (MPID = 8.6%; NPID = 50.2%) would belong to Group B and have intermediate levels of respiratory and fecal−oral transmission potentials, whereas other CoVs, such as porcine transmissible epidemic gastroenteritis virus (TGEV: MPID = 14%; NPID = 43%), were expected to be in Group C, which includes CoVs with lower respiratory but higher fecal−oral transmission potentials.[3,13] the MERS-CoV came in 2012−2013,14 which presented a great opportunity to test the validity of the disorder-based viral transmission model. The model placed MERS-CoV to the group C,15 and, the MERS-CoV reservoir was later found to be among farm animals including camels, which are highly associated with fecal−oral transmission.[14,16] MERS-CoV was found to be not transmissible among humans.[14,15]
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