Origin and transmission of SARS-CoV-2
The SARS-CoV-2 is a β-coronavirus, which is enveloped non-segmented positive-sense RNA virus (subgenus sarbecovirus, Orthocoronavirinae subfamily) [6]. Coronaviruses (CoV) are divided into four genera, including α−/β−/γ−/δ-CoV. α- and β-CoV are able to infect mammals, while γ- and δ-CoV tend to infect birds. Previously, six CoVs have been identified as human-susceptible virus, among which α-CoVs HCoV-229E and HCoV-NL63, and β-CoVs HCoV-HKU1 and HCoV-OC43 with low pathogenicity, cause mild respiratory symptoms similar to a common cold, respectively. The other two known β-CoVs, SARS-CoV and MERS-CoV lead to severe and potentially fatal respiratory tract infections [7]. It was found that the genome sequence of SARS-CoV-2 is 96.2% identical to a bat CoV RaTG13, whereas it shares 79.5% identity to SARS-CoV. Based on virus genome sequencing results and evolutionary analysis, bat has been suspected as natural host of virus origin, and SARS-CoV-2 might be transmitted from bats via unknown intermediate hosts to infect humans. It is clear now that SARS-CoV-2 could use angiotensin-converting enzyme 2 (ACE2), the same receptor as SARS-CoV [8], to infect humans (upper panel, Fig. 1).
Fig. 1 Viral and host factors that influence the pathogenesis of SARS-CoV-2. Bats are the reservoir of a wide variety of coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV) -like viruses. SARS-CoV-2 may originate from bats or unknown intermediate hosts and cross the species barrier into humans. Virus-host interactions affect viral entry and replication. Upper panel: Viral factor. SARS-CoV-2 is an enveloped positive single-stranded RNA (ssRNA) coronavirus. Two-thirds of viral RNA, mainly located in the first open reading frame (ORF 1a/b), encodes 16 non-structure proteins (NSPs). The rest part of the virus genome encodes four essential structural proteins, including spike (S) glycoprotein, small envelope (E) protein, matrix (M) protein, and nucleocapsid (N) protein, and also several accessory proteins. S glycoprotein of SARS-CoV-2 binds to host cell receptors, angiotensin-converting enzyme 2 (ACE2), that is a critical step for virus entry. The possible molecules facilitated membrane invagination for SARS-CoV-2 endocytosis are still unclear. Other virus proteins may contribute to pathogenesis. Host factors (Lower panel) can also influence susceptibility to infection and disease progression. The elderly and people with underlying disease are susceptible to SARS-CoV-2 and tend to develop into critical conditions. RBD, receptor-binding domain; HR1, heptad repeats 1; HR2, heptad repeats 2

Epidemiology − reservoirs and transmission
The epidemic of unknown acute respiratory tract infection broke out first in Wuhan, China, since 12 December 2019, possibly related to a seafood market. Several studies suggested that bat may be the potential reservoir of SARS-CoV-2 [9, 10]. However, there is no evidence so far that the origin of SARS-CoV-2 was from the seafood market. Rather, bats are the natural reservoir of a wide variety of CoVs, including SARS-CoV-like and MERS-CoV-like viruses [11–13]. Upon virus genome sequencing, the COVID-19 was analyzed throughout the genome to Bat CoV RaTG13 and showed 96.2% overall genome sequence identity [8], suggesting that bat CoV and human SARS-CoV-2 might share the same ancestor, although bats are not available for sale in this seafood market [14]. Besides, protein sequences alignment and phylogenetic analysis [15] showed that similar residues of receptor were observed in many species, which provided more possibility of alternative intermediate hosts, such as turtles, pangolin and snacks.
Human-to-human transmission of SARS-CoV-2 occurs mainly between family members, including relatives and friends who intimately contacted with patients or incubation carriers. It is reported [16] that 31.3% of patients recent travelled to Wuhan and 72.3% of patients contacting with people from Wuhan among the patients of non-residents of Wuhan. Transmission between healthcare workers occurred in 3.8% of COVID-19 patients, issued by the National Health Commission of China on 14 February 2020. By contrast, the transmission of SARS-CoV and MERS-CoV is reported to occur mainly through nosocomial transmission. Infections of healthcare workers in 33–42% of SARS cases and transmission between patients (62–79%) was the most common route of infection in MERS-CoV cases [17, 18]. Direct contact with intermediate host animals or consumption of wild animals was suspected to be the main route of SARS-CoV-2 transmission. However, the source(s) and transmission routine(s) of SARS-CoV-2 remain elusive.

Genome structure and key viral factors
Isolated from a COVID-19 pneumonia patient, a worker in the Wuhan seafood market, the complete genome of Wuhan-Hu-1 coronavirus (WHCV), one strain of SARS-CoV-2, is 29.9 kb [14]. While SARS-CoV and MERS-CoV have positive-sense RNA genomes of 27.9 kb and 30.1 kb, respectively [19]. It has been shown that the genome of CoVs contains a variable number (6–11) of open reading frames (ORFs) [20]. Two-thirds of viral RNA, mainly located in the first ORF (ORF1a/b) translates two polyproteins, pp1a and pp1ab, and encodes 16 non-structural proteins (NSP), while the remaining ORFs encode accessory and structural proteins. The rest part of virus genome encodes four essential structural proteins, including spike (S) glycoprotein, small envelope (E) protein, matrix (M) protein, and nucleocapsid (N) protein [21], and also several accessory proteins, that interfere with the host innate immune response. Wu et al. [14] have recently performed deep meta-transcriptomic sequencing on WHCV, which contained 16 predicted NSP. WHCV exhibits some genomic and phylogenetic similarity to SARS-CoV, particularly in the S-glycoprotein gene and receptor-binding domain (RBD), indicating the capability of direct human transmission. Compared with the known SARS-CoV and MERS-CoV genome, SARS-CoV-2 is closer to the SARS-like bat CoVs in terms of the whole genome sequence. Most genomic encoded proteins of SARS-CoV-2 are similar to SARS-CoVs, as well as exist certain differences. At the protein level, there are no amino acid substitutions that occurred in NSP7, NSP13, envelope, matrix, or accessory proteins p6 and 8b, except in NSP2, NSP3, spike protein, underpinning subdomain, i.e., RBD [22]. Another recent research suggested [23] that the mutation in NSP2 and NSP3 play a role in infectious capability and differentiation mechanism of SARS-CoV-2. This provokes people to explore the difference of the host tropism and transmission between SARS-CoV-2 and SARS-CoV or conduct further investigations on the potential therapeutic targets. Zhang et al. [24] analyzed the genotypes of COVID-19 in different patients from several provinces and found that SARS-CoV-2 had been mutated in different patients in China. Although the degree of diversification of SARS-CoV-2 is smaller than the mutation of H7N9 avian influenza [25]. Tang et al. [26] conducted a population genetic analyses of 103 SARS-CoV-2 genomes and classified out two prevalent evolvement types of SARS-CoV-2, L type (~ 70%) and S type (~ 30%). The strains in L type, derived from S type, are evolutionarily more aggressive and contagious. Thus, virologists and epidemiologists need to closely monitor the novel coronavirus, in order to inspect the virulence and epidemic.

Coronavirus replication and pathogenesis
ACE2, found in the lower respiratory tract of humans, is known as cell receptor for SARS-CoV [27] and regulates both the cross-species and human-to-human transmission [28]. Isolated from the bronchoalveolar lavage fluid (BALF) of a COVID-19 patient, Zhou et al. [8] have confirmed that the SARS-CoV-2 uses the same cellular entry receptor, ACE2, as SARS-CoV. The virion S-glycoprotein on the surface of coronavirus can attach to the receptor, ACE2 on the surface of human cells [29]. S glycoprotein includes two subunits, S1 and S2 [30]. S1 determines the virus-host range and cellular tropism with the key function domain − RBD, while S2 mediates virus-cell membrane fusion by two tandem domains, heptad repeats 1 (HR1) [31] and HR2 [32]. After membrane fusion, the viral genome RNA is released into the cytoplasm, and the uncoated RNA translates two polyproteins, pp1a and pp1ab [33], which encode non-structural proteins, and form replication-transcription complex (RTC) in double-membrane vesicle [34]. Continuously RTC replicate and synthesize a nested set of subgenomic RNAs [35], which encode accessory proteins and structural proteins. Mediating endoplasmic reticulum (ER) and Golgi [36], newly formed genomic RNA, nucleocapsid proteins and envelope glycoproteins assemble and form viral particle buds. Lastly, the virion-containing vesicles fuse with the plasma membrane to release the virus.
Because the binding of SARS-CoV-2 Spike (S) glycoprotein and ACE2 receptor is a critical step for virus entry, virus-receptor binding affinity is under intensive study through different approaches. Systematic detection of β-CoV receptors showed that human cells expressing ACE2, but not human Dipeptidyl peptidase-4 (DPP4) or APN (Aminopeptidase N), were enhanced entry of SARS-CoV-2 [37]. While, another study showed that S-protein and ACE2 binding efficiency is 10- to 20- fold higher than that of SARS-CoV, evidenced by Cryo-EM Structure of the SARS-CoV-2 Spike in the prefusion conformation [38]. For SARS-CoV, the cleavage of trimer S protein is triggered by the cell surface-associated transmembrane protease serine 2 (TMPRSS2) [39] and cathepsin [40], while the possible molecules facilitated membrane invagination for SARS-CoV-2 endocytosis are still unclear. Up to the date this review paper was prepared, reports showed that the SARS-CoV-2 may readily transmit, while cause less serious human infection rather than human SARS-CoV. Based on the latest WHO report, the number of infected people (over 80,000 globally, updated on 1 March 2020). The global outbreak may due to the following factors: firstly, the unknown pneumonia outbroke at the time of China Spring Festival, when the mass population flowing. Secondly, more detailed molecular mechanisms of viral binding and entry manners await to be elucidated, which may hamper the development of targeted therapy. Thirdly, available data suggested that the SARS-CoV-2 may be less virulent than the SARS-CoV and MERS-CoV, with the currently analyzed mortality of COVID-19 is 3.4%, lower than death rate of SARS (9.6%) and MERS (around 35%), respectively [19]. Thus, the potential mechanisms for human-to-human transmission and pathogenic mechanisms of the SARS-CoV-2 are under extensively studied.