Goh's BioComputing, Singapore 548957, Republic of Singapore,
Pac Symp Biocomput. 2021;26:143-153.
Several related viral shell disorder (disorder of shell proteins of viruses) models were built using a disorder predictor via AI. The parent model detected the presence of high levels of disorder at the outer shell in viruses, for which vaccines are not available. Another model found correlations between inner shell disorder and viral virulence. A third model was able to positively correlate the levels of respiratory transmission of coronaviruses (CoVs). These models are linked together by the fact that they have uncovered two novel immune evading strategies employed by the various viruses. The first involve the use of highly disordered "shape-shifting" outer shell to prevent antibodies from binding tightly to the virus thus leading to vaccine failure. The second usually involves a more disordered inner shell that provides for more efficient binding in the rapid replication of viral particles before any host immune response. This "Trojan horse" immune evasion often backfires on the virus, when the viral load becomes too great at a vital organ, which leads to death of the host. Just as such virulence entails the viral load to exceed at a vital organ, a minimal viral load in the saliva/mucus is necessary for respiratory transmission to be feasible. As for the SARS-CoV-2, no high levels of disorder can be detected at the outer shell membrane (M) protein, but some evidence of correlation between virulence and inner shell (nucleocapsid, N) disorder has been observed. This suggests that not only the development of vaccine for SARS-CoV-2, unlike HIV, HSV and HCV, is feasible but its attenuated vaccine strain can either be found in nature or generated by genetically modifying N.
利用 AI 中的无序预测器构建了几个相关的病毒外壳紊乱(病毒外壳蛋白紊乱)模型。原始模型在尚未有疫苗的情况下,在外壳检测到病毒中存在高水平的紊乱。另一个模型发现了内核紊乱与病毒毒力之间的相关性。第三个模型能够与冠状病毒(CoV)的呼吸道传播水平呈正相关。这些模型之间的联系在于,它们揭示了各种病毒使用的两种新的免疫逃避策略。第一种策略涉及使用高度无序的“形状变化”外壳,以防止抗体紧密结合病毒,从而导致疫苗失效。第二种策略通常涉及更无序的内核,从而在宿主免疫反应之前,在病毒颗粒的快速复制中提供更有效的结合。这种“特洛伊木马”免疫逃避策略通常会适得其反,当病毒在重要器官中的载量过大时,宿主会死亡。正如这种毒力需要病毒载量在重要器官中超过一定水平一样,在唾液/粘液中具有最小的病毒载量对于可行的呼吸道传播是必要的。对于 SARS-CoV-2,在外膜(M)蛋白中无法检测到高水平的无序,但已经观察到毒力与内核(核衣壳,N)无序之间存在相关性的一些证据。这表明,不仅 SARS-CoV-2 的疫苗开发不像 HIV、HSV 和 HCV 那样可行,而且其减毒疫苗株要么可以在自然界中找到,要么可以通过基因修饰 N 来产生。