# Causes and Consequences of Coronavirus Spike Protein Variability

## TL;DR

This paper reviews how changes in the SARS-CoV-2 Spike protein may have contributed to the spread and impact of the COVID-19 pandemic.

## Contribution

The paper provides a comprehensive review of host-driven adaptations in the Spike protein and their effects on virus behavior.

## Key findings

- SARS-CoV-2 Spike protein adaptations may enhance infectivity and immune evasion.
- Host factors influence Spike protein variability and virus transmission.
- Broad-spectrum therapeutics and vaccines are discussed for future pandemic preparedness.

## Abstract

Coronaviruses are a large family of enveloped RNA viruses found in numerous animal species. They are well known for their ability to cross species barriers and have been transmitted from bats or intermediate hosts to humans on several occasions. Four of the seven human coronaviruses (hCoVs) are responsible for approximately 20% of common colds (hCoV-229E, -NL63, -OC43, -HKU1). Two others (SARS-CoV-1 and MERS-CoV) cause severe and frequently lethal respiratory syndromes but have only spread to very limited extents in the human population. In contrast the most recent human hCoV, SARS-CoV-2, while exhibiting intermediate pathogenicity, has a profound impact on public health due to its enormous spread. In this review, we discuss which initial features of the SARS-CoV-2 Spike protein and subsequent adaptations to the new human host may have helped this pathogen to cause the COVID-19 pandemic. Our focus is on host forces driving changes in the Spike protein and their consequences for virus infectivity, pathogenicity, immune evasion and resistance to preventive or therapeutic agents. In addition, we briefly address the significance and perspectives of broad-spectrum therapeutics and vaccines.