Abstract
Human coronaviruses (HCoVs) are of zoonotic origins, and seven distinct HCoVs are currently known to infect humans. While the four seasonal HCoVs appear to be mildly pathogenic and circulate among human populations, the other three designated SARS-CoV, MERS-CoV, and SARS-CoV-2 can cause severe diseases in some cases. The newly identified SARS-CoV-2, a causative virus of COVID-19 that can be deadly, is now spreading worldwide much more efficiently than the other two pathogenic viruses. Despite evident differences in these properties, all HCoVs commonly have an exceptionally large genomic RNA with a rather peculiar gene organization and have the potential to readily alter their biological properties. CoVs are characterized by their biological diversifications, high recombination, and efficient adaptive evolution. We are particularly concerned about the high replication and transmission nature of SARS-CoV-2, which may lead to the emergence of more transmissible and/or pathogenic viruses than ever before. Furthermore, novel variant viruses may appear at any time from the CoV pools actively circulating or persistently being maintained in the animal reservoirs, and from the CoVs in infected human individuals. In this review, we describe knowns of the CoVs and then mention their unknowns to clarify the major issues to be addressed. Genome organizations and sequences of numerous CoVs have been determined, and the viruses are presently classified into separate phylogenetic groups. Functional roles in the viral replication cycle in vitro of non-structural and structural proteins are also quite well understood or suggested. In contrast, those in the in vitro and in vivo replication for various accessory proteins encoded by the variable 3′ one-third portion of the CoV genome mostly remain to be determined. Importantly, the genomic sequences/structures closely linked to the high CoV recombination are poorly investigated and elucidated. Also, determinants for adaptation and pathogenicity have not been systematically investigated. We summarize here these research situations. Among conceivable projects, we are especially interested in the underlying molecular mechanism by which the observed CoV diversification is generated. Finally, as virologists, we discuss how we handle the present difficulties and propose possible research directions in the medium or long term.
Highlights
People around the world have been seeing a global devastating outbreak of COVID-19, caused by a new human coronavirus (HCoV) designated severe acute respiratory syndrome CoV 2 (SARS-CoV-2) (Lu et al, 2020; Wu A. et al, 2020; Zhu et al, 2020)
Various CoVs were isolated from mammals and birds, and were long considered to be weakly pathogenic until the identification of SARS-CoV (Drosten et al, 2003; Fouchier et al, 2003; Ksiazek et al, 2003; Zhong et al, 2003) followed by the Middle East respiratory syndrome virus MERS-CoV (Zaki et al, 2012) as a causative virus for serious human infectious disease
As for the origin and evolution of the seven HCoVs (Figure 1) described above, researchers have sufficiently clarified this particular subject by their extensive efforts through field and in silico analyses (Su et al, 2016; Forni et al, 2017; Cui et al, 2019; Adachi et al, 2020; Biswas et al, 2020; Tang D. et al, 2020; Ye et al, 2020)
Summary
People around the world have been seeing a global devastating outbreak of COVID-19, caused by a new human coronavirus (HCoV) designated severe acute respiratory syndrome CoV 2 (SARS-CoV-2) (Lu et al, 2020; Wu A. et al, 2020; Zhu et al, 2020). A number of human coronaviruses were discovered and found to be responsible for a seasonally prevalent viral disease with mild symptoms such as the common cold and/or diarrhea (Forni et al, 2017; de Wilde et al, 2018; Cui et al, 2019; Tse et al, 2020; Wang N. et al, 2020; Ye et al, 2020) The selected subjects should be experimentally and conclusively analyzed by molecular genetic methods of the day to obtain definitive answers
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