Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Jiao-Mei Huang; Syed Sajid Jan; Xiaobin Wei; Yi Wan; Songying Ouyang

The family Coronaviridae is comprised of large, enveloped, single stranded, and positivesense RNA viruses that can infect a wide range of animals including humans Guan et al., 2003) . The viruses are further classified into four genera: alpha, beta, gamma, and delta coronavirus (King et al., 2012) . So far, all coronaviruses (CoVs) identified in human belong to the genera alpha and beta. Among them betaCoVs are of particular importance. Different novel strains of highly infectious betaCoVs have been emerged in human populations in the past two decades that have caused severe health concern all over the world. Severe acute respiratory syndrome coronavirus (SARS-CoV) was first recognized in 2003, causing a global outbreak (Zhong, 2004; Peiris et al., 2004; Cherry, 2004) . It was followed by another pandemic event in 2012 by a novel strain of coronavirus designated as Middle East respiratory syndrome coronavirus (MERS-CoV) (Lu et al., 2013) . Both CoVs were zoonotic pathogens and evolved in animals. Bats in the genus Rhinolophus are natural reservoir of coronaviruses worldwide, and it is presumed that both SARS-CoV and MERS-CoV have been transmitted to human through some intermediate mammalian hosts (Li et al., 2005a; Bolles et al., 2011; Al-Tawfiq and Memish, 2014 The large trimeric spike glycoprotein (S) located on the surface of CoVs is crucial for viral infection and pathogenesis, which is further subdivided into N-terminal S1 subunit and C-terminal S2 domain. The S1 subunit is specialized in recognizing receptors on host cell, comprising of two separate domains located at N-and C-terminal which can fold independently and facilitate receptor engagement (Masters, 2006) . Receptor-binding domains (RBDs) of most CoVs are located on S1 C-terminus and enable attachment to its host receptor (Li et al., 2005b) . The host specificity of virus particle is determined by amino acid sequence of RBD and is usually dissimilar among different CoVs. Therefore, RBD is a core determinant for tissue tropism and host range of CoVs. This article presents SARS-CoV-2 phylogenetic trees, comparison and analysis of genome, spike protein, and RBD amino acid sequences of different CoVs, deducing source and etiology of COVID-19 and evolutionary relationship among SARS-CoV-2 in human.