Nanomechanical Analysis of Coronavirus Spike proteins and Correlation with Infectivity and Lethality

Abstract

The novel coronavirus disease, COVID-19, has spread rapidly around the world. Its causative virus, SARS-CoV-2, enters human cells through the physical interaction between the receptor-binding domain (RBD) of its spike protein and the human cell receptor ACE2. As an increasing number of variants of SARS-CoV-2 circulates globally, estimates of infectiousness and lethality of newly emerging strains are important. Here, we provide a novel way to develop a deeper understanding of coronavirus spike proteins, connecting their nanomechanical features – specifically the vibrational spectrum and quantitative measures of mobility – with virus lethality and infection rate. The key result of our work is that both, the overall flexibility of upward RBD and the mobility ratio of RBDs in different conformations, represent two significant factors that show a positive scaling with virus lethality and an inverse correlation with the infection rate. A quantitative model is presented to make predictions on the infectivity and lethality of SARS-CoV-2 variants based on molecular motions and vibrational patterns of the virus spike protein. Our analysis shows that epidemiological virus properties can be linked directly to pure nanomechanical, vibrational aspects, offering an alternative way of screening new viruses and mutations against high threat levels, and potentially exploring novel ways to prevent infections from occurring by interfering with the nanoscale motions.