Abstract
The SARS-CoV-2 Spike protein needs to be in an open-state conformation to interact with ACE2 to initiate viral entry. We utilise coarse-grained normal mode analysis to model the dynamics of Spike and calculate transition probabilities between states for 17081 variants including experimentally observed variants. Our results correctly model an increase in open-state occupancy for the more infectious D614G via an increase in flexibility of the closed-state and decrease of flexibility of the open-state. We predict the same effect for several mutations on glycine residues (404, 416, 504, 252) as well as residues K417, D467 and N501, including the N501Y mutation recently observed within the B.1.1.7, 501.V2 and P1 strains. This is, to our knowledge, the first use of normal mode analysis to model conformational state transitions and the effect of mutations on such transitions. The specific mutations of Spike identified here may guide future studies to increase our understanding of SARS-CoV-2 infection mechanisms and guide public health in their surveillance efforts.
Highlights
The coronavirus pandemic has emerged as a major and urgent issue affecting individuals, families and society as a whole
The A222V mutation, reportedly responsible for many infections, emerged in Spain during the Summer of 2020 and since has spread to neighbor countries [54]; In Denmark, new strains related to SARS-CoV-2 transmission in mink farms were confirmed in early October by the World Health Organization (WHO) and shown to be caused by specific mutations not previously observed with the novelty of backand-forth transmission between minks and humans [63]
Such occurrences point to the possibility that new mutations in SARSCoV-2 may bring about more infectious strains
Summary
The coronavirus pandemic has emerged as a major and urgent issue affecting individuals, families and society as a whole. Among all outbreaks of aerosol transmissible diseases in the 21st century, the COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus [1,2], has the highest infection and death cumulative numbers—61 million infections and over 1.4 million deaths, according to the World Health Organization (WHO) epidemiological report of December 1, 2020 [3]. In 2003 the SARS coronavirus (SARS-CoV) pandemic caused 8,098 infections and 774 deaths before it was brought under control [4,5]. In 2012, the Middle East respiratory syndrome-related coronavirus (MERS-CoV) outbreak caused 2499 infections and 858 deaths, presenting the highest fatality rate [6]. SARS-CoV-2, SARS-CoV and MERSCoV, as coronaviruses in general, present considerable mutation rates, which may contribute to future outbreaks. The high mutation rate may in part be responsible for the zoonotic nature of these viruses and points to a clear risk of stillundetected additional members of the coronavirideae family of viruses making the jump from their traditional hosts to humans in the future
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