Toward Understanding Molecular Bases for Biological Diversification of Human Coronaviruses: Present Status and Future Perspectives

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.

Genomic surveillance of SARS-CoV-2 tracks early interstate transmission of P.1 lineage and diversification within P.2 clade in Brazil

“…The copyright holder for this preprint this version posted March 25, 2021. ; https://doi.org/10.1101/2021.03.21.21253418 doi: medRxiv preprint differentiated in several subclades between April and September of 2020 (Figure 3), all of them present in many states. The occurrence of P.2 subclades, in practice, means that epidemiological parameters, such as transmission rate, lethality, and immune response escape may vary within the lineage, hindering its containment [32]. If uncontrolled, the expected evolutionary course is for these subclades to evolve into whole lineages with exclusive mutations.…”

HCoV-NL63 and SARS-CoV-2 Share Recognized Epitopes by the Humoral Response in Sera of People Collected Pre- and during CoV-2 Pandemic

“…The known human CoVs (HCoVs) are HCoV- 229E and HCoV-NL63 belonging to the alpha group and HCoV-OC43 within the beta group, are generally recognized to cause mild upper respiratory tract diseases and, rarely, lower respiratory tract diseases. However, HCoV-NL63 is the only CoV responsible of mild infections that use the ACE2 receptor as target for its S protein [ 20 ].…”

The role of airborne particles and environmental considerations in the transmission of SARS-CoV-2

“…SARS-CoV-2 and SARS-CoV-1 have similar receptor binding domains but SARS-CoV-2 and BatCoV RaTG13 receptor binding domains have low similarity, indicating that there is an intermediate host between bats and humans ( Wong et al, 2020a ). In terms of mortality, SARS-CoV-2 is less deadly but far more transmissible than SARS-CoV-1 ( Koma et al, 2020 , Petersen et al, 2020 ). The mortalities caused by COVID-19 vary between countries.…”