Understanding Human Coronavirus HCoV-NL63

Abdul-Rasool, Sahar; Fielding, Burtram C

Molecular clock analysis is the average rate at which a species' genome accumulates mutations and is used to measure that species' evolutionary divergence. The reliability of molecular dating is dependent on the validity of the molecular clock hypothesis, which assumes that the substitution rate is roughly constant [83] , with an average substitution rate for coronaviruses estimated to be 10 4 substitutions per year per site [84, 85] . With the lack of sufficient sequence data available for HCoV-NL63, the substitution rate for HCoV-229E, using partial sequences of the S gene from different known dates, was calculated. Then, assuming a constant evolutionary rate in time and a constant evolutionary rate between the branches for HCoV-NL63 and HCoV229E, the time to their most recent common ancestor was dated to the 11 th century [24] . This shows that HCoV-NL63 has been present in the human population for centuries. In support of this finding, the virus described by Fouchier et al. was originally isolated from an eight-month old child in 1988 [19] . More recent studies in the Netherlands also supported the notion that only SARS-CoV has recently been introduced to the human population from an animal source, while HCoV-NL63 has been circulating in humans for a while [86] . With the exception of SARS-CoV, the coronaviruses infecting humans are not well studied. This is partly due to the prevailing view that they are only involved in mild respiratory tract infections. The introduction of sensitive molecular and cell biology techniques have aided in identifying three 'new' human coronaviruses, which has improved our understanding of the classification of the coronaviruses. These modern tools now need to be developed further to make the sensitive and accurate detection of coronaviruses in clinical samples possible. This would increase our understanding of the extent to which coronaviruses affect human health. Importantly, Donaldson and colleagues has recently reported the assembly of a full-length infectious HCoV-NL63 clone, which will make the study of this virus easier, improving our understanding of the role of each of the proteins encoded by the HCoV-NL63 genome [87] . In the long run, molecular and cell biology tools could help elucidate the link, if any, between human coronaviruses and human diseases of the respiratory tract, the vascular system, the central nervous system and the gastrointestinal tract [82] . author whose work was inadvertently omitted from this review.