The S protein promotes entry into the host cell by binding to the receptor angiotensin-converting enzyme 2 (ACE2) ( Walls et al., 2020), a cell surface enzyme with transcripts present in the lungs, heart, kidney, alveolar epithelial type 2 cells, and intestine ( Donoghue et al., 2000 Zhang et al., 2020). The S protein consists of two subunits S1, which is responsible for membrane binding ( Millet and Whittaker, 2018), and S2 for membrane fusion ( Li, 2012 Heald-Sargent and Gallagher, 2012 Wu et al., 2004). Increasing evidence has shown the role of S protein in binding with the host receptor and subsequent viral entry causing COVID-19 ( Belouzard et al., 2012 Li, 2016). The S proteins of SARS-CoVs are critical for host cell recognition, entry, and infections ( Shang et al., 2020). Several molecular factors have contributed to increase the infectivity of SARS-CoV-2, particularly the recombination events in the S gene, which encodes the S glycoprotein ( Hu et al., 2017). In contrast to the earlier SARS and MERS outbreaks, the SARS-CoV-2 outbreak has proven to be highly infectious ( World Health Organization, 2021 Lu et al., 2015) and global in nature. SARS-CoV-2 shares ∼79% nucleotide sequence identity to SARS-CoV ( Zhou et al., 2020) and is even more similar to several bat CoVs ( Chen et al., 2020 Zhou et al., 2020). Thus, a comprehensive analysis of SARS-CoV 2 across diverse host species may help determine their diversity and transmissibility of COVID-19. However, the steps involved in the natural selection and adaptability of SARS-CoV-2 to its human host from animals remains unclear. The continued evolution and genetic diversity in variants of SARS-CoV have increased the possibility of crossing the species barrier and transmission of disease to humans ( Li et al., 2005b). SARS-CoV was transmitted to humans from exotic animals ( Guan et al., 2003), whereas MERS was transmitted from dromedary camels ( Sabir et al., 2016) with bats being the primary reservoir for both viruses ( Cui et al., 2019 Perlman, 2020). ![]() These CoVs are single-stranded positive-sense RNA viruses belonging to the Coronaviridae family ( Gorbalenya et al., 2020) and infect both animals (bats, snakes, pangolin, etc.) and humans ( Jones et al., 2008 Karesh et al., 2012 Cleaveland et al., 2001). COVID-19 is the third outbreak of coronavirus (CoV) associated disease in the past 100 years the first two epidemics were severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS), respectively. Despite the implementation of effective vaccines to control COVID-19, mutations in the SARS-CoV-2 genome, particularly in the spike (S) protein, led to emergence of variants against which the current vaccines may be partially effective. The World Health Organization has reported nearly 178 million confirmed cases and 3,864,180 deaths globally as of J( World Health Organization, 2021). The outbreak of SARS-CoV-2 in the city of Wuhan, China, in 2019 led to the coronavirus disease-2019 (COVID-19) pandemic causing millions of deaths worldwide. We suggest that alterations of these amino acids between human and animal coronaviruses may provide insights into the development and transmission of SARS-CoV-2 in human and other species and support the discovery of targeted antiviral therapies. SPIKES identified 20 informative physicochemical properties of the spike protein, including information measures for alpha helix and relative mutability, and amino acid and dipeptide compositions, which have shown compositional difference at the amino acid sequence level between human and diverse animal coronaviruses. Here, we propose a spike protein predictor SPIKES incorporating with an inheritable bi-objective combinatorial genetic algorithm to identify the biochemical properties of spike proteins and determine their specificity to human hosts. ![]() Knowledge of the host-specific properties of the spike protein is of crucial importance to understand the adaptability of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to infect multiple species and alter transmissibility, particularly in humans.
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