Toward Understanding Molecular Bases for Biological Diversification of Human Coronaviruses: Present Status and Future Perspectives
FRONTIERS IN MICROBIOLOGY
Authors: Koma, Takaaki; Adachi, Shun; Doi, Naoya; Adachi, Akio; Nomaguchi, Masako
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 cyclein vitroof non-structural and structural proteins are also quite well understood or suggested. In contrast, those in thein vitroandin vivoreplication 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.
Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics
LANCET INFECTIOUS DISEASES
Authors: Petersen, Eskild; Koopmans, Marion; Go, Unyeong; Hamer, Davidson H.; Petrosillo, Nicola; Castelli, Francesco; Storgaard, Merete; Al Khalili, Sulien; Simonsen, Lone
Abstract
The objective of this Personal View is to compare transmissibility, hospitalisation, and mortality rates for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with those of other epidemic coronaviruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and pandemic influenza viruses. The basic reproductive rate (R-0) for SARS-CoV-2 is estimated to be 2.5 (range 1.8-3.6) compared with 2.0-3.0 for SARS-CoV and the 1918 influenza pandemic, 0.9 for MERS-CoV, and 1.5 for the 2009 influenza pandemic. SARS-CoV-2 causes mild or asymptomatic disease in most cases; however, severe to critical illness occurs in a small proportion of infected individuals, with the highest rate seen in people older than 70 years. The measured case fatality rate varies between countries, probably because of differences in testing strategies. Population-based mortality estimates vary widely across Europe, ranging from zero to high. Numbers from the first affected region in Italy, Lombardy, show an all age mortality rate of 154 per 100 000 population. Differences are most likely due to varying demographic structures, among other factors. However, this new virus has a focal dissemination; therefore, some areas have a higher disease burden and are affected more than others for reasons that are still not understood. Nevertheless, early introduction of strict physical distancing and hygiene measures have proven effective in sharply reducing R-0 and associated mortality and could in part explain the geographical differences.