Chen Jiahui, Wang Rui, Wei Guo-Wei
Department of Mathematics, Michigan State University, MI 48824, USA.
Department of Electrical and Computer Engineering, Michigan State University, MI 48824, USA.
ArXiv. 2021 Sep 15:arXiv:2109.08148v1.
The mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution and transmission is elusive and its understanding, a prerequisite to forecast emerging variants, is of paramount importance. SARS-CoV-2 evolution is driven by the mechanisms at molecular and organism scales and regulated by the transmission pathways at the population scale. In this review, we show that infectivity-based natural selection was discovered as the mechanism for SARS-CoV-2 evolution and transmission in July 2020. In April 2021, we proved beyond all doubt that such a natural selection via infectivity-based transmission pathway remained the sole mechanism for SARS-CoV-2 evolution. However, we reveal that antibody-disruptive co-mutations [Y449S, N501Y] on the spike protein receptor-binding domain (RBD) debuted as a new vaccine-resistant transmission pathway of viral evolution in highly vaccinated populations a few months ago. Over one year ago, we foresaw that mutations on RBD residues, 452 and 501, would "both have high chances to mutate into significantly more infectious COVID-19 strains". Mutations on these residues underpin prevailing SARS-CoV-2 variants Alpha, Beta, Gamma, Delta, Epsilon, Theta, Kappa, Lambda, and Mu at present and are expected to be vital to emerging variants in the future. We anticipate that viral evolution will combine RBD co-mutations at these two sites, creating future variants that are about ten times more infectious than the original SARS-CoV-2. Additionally, two complementary transmission pathways of viral evolution, i.e., infectivity and vaccine resistance will prolong our battle with COVID-19 for years. We predict that RBD co-mutation sets [A411S, L452R, T478K], [L452R, T478K, N501Y], [L452R, T478K, E484K, N501Y], [K417N, L452R, T478K], and [P384L, K417N, E484K, N501Y] will have a high chance to grow into dominating variants due to their high infectivity and/or strong ability to break through current vaccines, calling for the development of new vaccines and antibody therapies.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的进化和传播机制尚不清楚，而了解这一点是预测新出现变体的先决条件，至关重要。SARS-CoV-2的进化由分子和生物体尺度的机制驱动，并受群体尺度的传播途径调控。在本综述中，我们表明基于感染性的自然选择在2020年7月被发现是SARS-CoV-2进化和传播的机制。2021年4月，我们确凿地证明，通过基于感染性的传播途径进行的这种自然选择仍然是SARS-CoV-2进化的唯一机制。然而，我们发现刺突蛋白受体结合域（RBD）上的抗体干扰性共突变[Y449S, N501Y]几个月前在高疫苗接种人群中作为病毒进化的一种新的抗疫苗传播途径首次出现。一年多以前，我们就预见到RBD残基452和501上的突变“都很有可能突变为传染性更强的新冠病毒毒株”。这些残基上的突变是目前流行的SARS-CoV-2变体Alpha、Beta、Gamma、Delta、Epsilon、Theta、Kappa、Lambda和Mu的基础，预计对未来新出现的变体也至关重要。我们预计病毒进化将结合这两个位点的RBD共突变，产生比原始SARS-CoV-感染性高约十倍的未来变体。此外，病毒进化的两种互补传播途径，即感染性和疫苗抗性，将使我们与新冠疫情的斗争持续数年。我们预测RBD共突变集[A411S, L452R, T478K]、[L452R, T478K, N501Y]、[L452R, T478K, E484K, N501Y]、[K得发展新疫苗和抗体疗法。 2
