key: cord-0993939-475nei28 authors: Li, Xingguang; Zai, Junjie; Wang, Xiaomei; Li, Yi title: Potential of large “first generation” human‐to‐human transmission of 2019‐nCoV date: 2020-02-14 journal: J Med Virol DOI: 10.1002/jmv.25693 sha: 6737f768a5188a131d0a6e819098b9461dd1972f doc_id: 993939 cord_uid: 475nei28 To investigate the genetic diversity, time origin, and evolutionary history of the 2019‐nCoV outbreak in China and Thailand, a total of 12 genome sequences of the virus with known sampling date (24 December 2019 and 13 January 2020) and geographic location (primarily Wuhan city, Hubei Province, China, but also Bangkok, Thailand) were analyzed. Phylogenetic and likelihood‐mapping analyses of these genome sequences were performed. On the basis of our results, the star‐like signal and topology of 2019‐nCoV may be indicative of potentially large “first generation” human‐to‐human virus transmission. We estimated that 2019‐nCoV likely originated in Wuhan on 9 November 2019 (95% credible interval: 25 September 2019 and 19 December 2019), and that Wuhan is the major hub for the spread of the 2019‐nCoV outbreak in China and elsewhere. Our results could be useful for designing effective prevention strategies for 2019‐nCoV in China and beyond. which also includes the viruses responsible for the Middle East respiratory syndrome (MERS). 4, 5 Field studies have revealed the original source of SARS-CoV and MERS-CoV to be the bat, 6-9 with masked palm civets (a mammal native to Asia and Africa) [10] [11] [12] and camels, 13, 14 respectively, serving as intermediate hosts between bats and humans. To date, 2019-nCoV is most closely associated with SARS and related viruses that circulate in bats. 15 The hypothesis that 2019-nCoV jumped from an animal at the Wuhan Huanan Seafood Wholesale Market, which sold processed meats and live consumable animals, is strongly supported by previous study suggesting that this virus came directly or indirectly from bats. 15 Therefore, the 2019-nCoV outbreak implies that the human consumption of wild animals should be limited to prevent zoonotic disease infection. Professor Zhong Nanshan, a SARS intervention specialist, is the respiratory researcher leading the Chinese government's expert panel on the 2019-nCoV outbreak. After a visit to Wuhan city on 20 January 2020, Professor Zhong confirmed that 2019-nCoV is spreading between people, and further confirmed that 14 medical January 2020) (Table S1 ). For this dataset, the 2019-nCoV genome sequences were aligned using MAFFT v7.222 16 and then manually curated using BioEdit v7.2.5. 17 To study the amount of evolutionary information contained in the dataset, likelihood-mapping analysis 18 As no temporal signal was present in the dataset, we employed HKY+G, as well as a constant size coalescent tree prior and strict molecular clock model assuming an evolutionary rate of 4.59 × 10 −4 substitutions per site per year to estimate the time to most recent common ancestor (TMRCA) for this dataset based on previous genetic analysis. 23 We also To perform ancestral reconstruction of the unobserved sampling locations (k = 2), discrete phylogeographic analyses 28 were performed using the empirical tree distributions generated for our 2019-nCoV dataset. The location exchange process was modeled using asymmetric continuous-time Markov chains (CTMC) 28 with an approximate CTMC conditional reference prior to the overall rate scaler and a uniform prior distribution. Bayesian analysis was run using BEAST v1.8.4 21 To identify a subset of well-supported migration events among 2019-nCoV strains, we used a Bayesian stochastic search variable selection procedure with a hierarchical prior on location indicators (0-1), which allow CTMC rates to shrink to zero with some probability, using BEAST v1.8.4. 21 Strongly supported rates of virus movement (Bayes factor > 10) were identified using SpreaD3 v0.9.6. 29 3 | RESULTS The dataset included 12 genome sequences of 2019-nCoV strains from Wuhan, China (n = 10), with sampling dates between 24 and 30 December 2019, and from Bangkok, Thailand (n = 2), with sampling date between 8 and 13 January 2020 (Table S1 ). The samples were primarily from Wuhan (83.33%), which is also the city of the original 2019-nCoV outbreak. EPI_ISL_402119, EPI_ISL_402120, EPI_ISL_402121: Originating and submitting lab-National Institute for Viral Dis- Identification of a novel coronavirus in patients with severe acute respiratory syndrome A previously undescribed coronavirus associated with respiratory disease in humans A novel coronavirus associated with severe acute respiratory syndrome Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia Middle East respiratory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group Ecoepidemiology and complete genome comparison of different strains of severe acute respiratory syndromerelated Rhinolophus bat coronavirus in China reveal bats as a reservoir for acute, self-limiting infection that allows recombination events Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats Bats are natural reservoirs of SARS-like coronaviruses Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human Molecular evolution of the SARS coronavirus during the course of the SARS epidemic in China SARS-CoV infection in a restaurant from palm civet MERS coronavirus neutralizing antibodies in camels MERS coronaviruses in dromedary camels A pneumonia outbreak associated with a new coronavirus of probable bat origin MAFFT multiple sequence alignment software version 7: improvements in performance and usability BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT Maximum-likelihood analysis using TREE -PUZZLE TREE-PUZZLE: maximum likelihood phylogenetic analysis using quartets and parallel computing New algorithms and methods to estimate maximumlikelihood phylogenies: assessing the performance of PhyML 3.0 Bayesian phylogenetics with BEAUti and the BEAST 1.7 Many-core algorithms for statistical phylogenetics Correction: MERS-CoV spillover at the camel-human interface. eLife Moderate mutation rate in the SARS coronavirus genome and its implications Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study Spread, circulation, and evolution of the Middle East respiratory syndrome coronavirus Posterior summarization in Bayesian phylogenetics using Tracer 1.7 Bayesian phylogeography finds its roots Interactive visualization of spatiotemporal history and trait evolutionary processes Potential of large "first generation" human-to-human transmission of 2019-nCoV