Abstract
Severe acute respiratory syndrome virus 2 (SARS-CoV2) has infected an estimated 400 million people world-wide, causing approximately 6 million deaths from severe coronavirus disease 2019 (COVID-19). The SARS-CoV2 Spike protein plays a critical role in viral attachment and entry into host cells. The recent emergence of highly transmissible variants of SARS-CoV2 has been linked to mutations in Spike. This review provides an overview of the structure and function of Spike and describes the factors that impact Spike’s ability to mediate viral infection as well as the potential limits to how good (or bad) Spike protein can become. Proposed here is a framework that considers the processes of Spike-mediated SARS-CoV2 attachment, dissociation, and cell entry where the role of Spike, from the standpoint of the virus, is to maximize cell entry with each viral-cell collision. Key parameters are identified that will be needed to develop models to identify mechanisms that new Spike variants might exploit to enhance viral transmission. In particular, the importance of considering secondary co-receptors for Spike, such as heparan sulfate proteoglycans is discussed. Accurate models of Spike-cell interactions could contribute to the development of new therapies in advance of the emergence of new highly transmissible SARS-CoV2 variants.
Highlights
Severe acute respiratory syndrome virus 2 (SARS-CoV2) has infected an estimated 400 million people world-wide, causing approximately 6 million deaths from severe coronavirus disease 2019 (COVID-19)
While the mechanism of viral infection involves a vast number of variables, the SARS-CoV2 Spike protein is one well-defined component that plays a critical role in viral attachment and entry into host cells [1]
In addition to the mutations characterized in the receptor binding domain (RBD) in Spike variants, the Alpha Delta and Omicron Spike proteins all contain a proline to arginine substitution at position 681 that has been reported to improve the efficiency of furin cleavage
Summary
Severe acute respiratory syndrome virus 2 (SARS-CoV2) has infected an estimated 400 million people world-wide, causing approximately 6 million deaths from severe coronavirus disease 2019 (COVID-19) (https://covid19.who.int, accessed on 1 March 2022). The world has already experienced several major waves of infection with the rise of the highly contagious and virulent Delta variant (B.1.1.617.2) in the late summer of 2021, and with the emergence of the even more highly transmissible Omicron variant (B.1.1.529). The wide distribution of effective vaccines coupled with the observation that the Omicron variant appears to cause less severe disease has led to a significantly reduced case-fatality rate with the Omicron variant compared to Delta. The high rate of infection with Omicron presents the possibility that new, more virulent strains of SARS-CoV2 will develop, which raises the question of whether there is a limit to how infectious this virus can become. This review will focus on the factors that impact Spike protein function and will discuss the theoretical limits to how good (or bad) Spike protein can become
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