key: cord-007926-um2khqhn
authors: Zhang, Jiahao; Ma, Kaixiong; Li, Huanan; Liao, Ming; Qi, Wenbao
title: The continuous evolution and dissemination of 2019 novel human coronavirus
date: 2020-02-22
journal: J Infect
DOI: 10.1016/j.jinf.2020.02.001
sha: 
doc_id: 7926
cord_uid: um2khqhn

nan

-S3). The overall genome identity of the 2019-nCoV and SARSr-CoV was ranging from 82% to 89%. With rapid dissemination of the 2019-nCoV, the viruses had been transmitted rapidly in more than 25 countries, and a steep increase in human infection with the 2019-nCoV occurred in China ( Fig. 1 ) . To further explore the genetic evolution of the 2019-nCoV, phylogenic relationships of 31 isolates examined in this study were explored and divided into four genotypes, including G1, G2, G3, and G4. We found that 25 isolates clustered together and had been circulating in Thailand and multiple provinces (e.g. Taiwan, Guangdong, Zhejiang, and Hubei) of China, suggestive of the ongoing co-circulation of the viruses. The 2019-nCoV circulating in USA and Wuhan, China clustered into an independent cluster. However, interestingly, the SZTH-0 02, 20SF013, and SZTH-0 01 strains in Guangdong province were located at basal branch of the 2019-nCoV ( Fig. 2 ) , indicative of a single origin. The genetic diversity of RNA-dependent RNA polymerase of the 2019-nCoV was very small (Supplementary Figure S1 ). By contrast, the Spike (S) genes of some 2019-nCoV prevailing in Guangdong province were found at the root of the 2019-nCoV in Wuhan (Supplementary Figure S2) . These findings indicated that the 2019-nCoV were infected from different regions in Wuhan and had been undergoing continuous evolution and dissemination in different regions. Compared with the rapid mutation of the influenza A viruses, the degree of diversification of the 2019-nCoV was much smaller. Nevertheless, we cannot rule out if the 2019-nCoV continue evolving to become more transmissible and virulent in humans in the near future.

The S protein mediates receptor binding and membrane fusion, and of particular note, it is of great importance to determine host tropism and transmission capacity. 5 Zhou et al. demonstrated that the 2019-nCoV use the same cell entry receptor, ACE2, as SARS-CoV. 6 The receptor binding region of the 2019-nCoV was more similar to that of SARS-CoV; however, we found that four amino acid substitutions in the receptor binding region of the 2019-nCoV, including S486Q, F485Y, N493G, and Y501V substitutions (2019-nCoV numbering), were different from that of SARS-CoV ( Fig. 2 ) , which might affect the receptor binding ability.

Bats provide a rich "gene pool" for interspecies exchange of genetic fragments of CoV. 7 Continuous surveillance in bats provide us a clue to the correlation between the 2019-nCoV and the animal origin CoV. Despite the shared cluster between the 2019-nCoV and bat SARSr-CoV, we cannot infer that the reservoir of the 2019-nCoV was originated from bats. Most of the patients infected with novel 2019-nCoV had a history to the seafood and live animal markets, and the vendor used to sale wild animal species, including marmot, snake, leopard cat, bamboo rat, badger, and hedgehog in Huanan seafood wholesale market (Supplementary Figure S4 ), all of which were susceptible to the novel CoV in nature, indicating that it remains likely there was intermediate hosts in the transmission cascade from bats to humans ( Fig. 2 ) . However, a question of a public health interest is which intermediate hosts harbor the 2019-nCoV that could infect humans, which should be examined in greater detail. Recently, the continuous interspecies transmission events of CoV occurred, including the emergence of MERS-CoV from camels to humans and swine acute diarrhea syndrome CoV from bat to swine, posing serious threats to public health. 8 , 9 With the tradition of feeding wild animals for food or use in traditional medicine in China, wild birds, mammals, and reptiles carrying the novel zoonotic viruses flowed frequently in trading center, which had considerable potential to transmit to humans of emerging viruses.

In 2018, China had participated a Global Virome Project to identify unknown viruses from wildlife to better prepare for the epidemics of infectious diseases in humans. 10 With multiple species of CoV circulating in different animal species that could be transmitted to humans, no one knows when or where the next outbreak will occur. Nevertheless, decreasing the risk for the spread of novel viruses including reducing contact among humans and wild ani- mal species and stopping novel viruses at their origins is urgently needed. We call upon wildlife biologists, ecologists, doctors, and veterinarians should promote exchange and share data across disciplines as a mean to minimize the potential for pandemics of the 2019-nCoV.

All authors have no potential conflicts of interest to disclose.

Emergence of SARS-like Coronavirus poses new challenge in China

Epidemiology, genetic recombination, and pathogenesis of coronaviruses

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-toperson transmission: a study of a family cluster

Bat-to-human: spike features determining 'host jump' of coronaviruses SARS-CoV, MERS-CoV, and beyond

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of Sars coronavirus

Vaccine against Middle East respiratory syndrome coronavirus

Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin

The global virome project

We sincerely thank the authors of the human 2019 coronavirus from GISAID EpiFlu TM Database. This work was supported by the National Natural Science Foundation of China ( 31941014 , 31830097 , 

Supplementary material associated with this article can be found, in the online version, at doi: 10.1016/j.jinf.2020.02.001 .
