PMC:7712180 / 60441-65991
Annnotations
{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/7712180","sourcedb":"PMC","sourceid":"7712180","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7712180","text":"4.3.3. β2 SARS-CoV-2\nSARS-CoV-2, which shares about 80% nt sequence identity with its elder cousin SARS-CoV [221], causes an acute respiratory disease that was officially named coronavirus disease 2019 (COVID-19). It is a novel coronavirus (2019-nCoV) that was first recognized in December 2019 in Wuhan, Hubei in Central China [222]. Different from SARS-CoV, with a mortality rate of 9.6% in cases of infection, SARS-CoV-2 generally causes mild to moderate disease, but it can also lead to severe disease and death in some cases [223,224]. Keeping the infected hosts alive enabled SARS-CoV-2 to adapt to humans with efficient human-to-human transmission. It spread rapidly worldwide, finally causing the COVID-19 pandemic, with outbreaks sustained in more than one WHO region [154], on 11 March 2020. As of 8 September 2020, the pandemic is ongoing and has caused 27,205,275 confirmed cases reported from 182 countries and 33 territories and reported from international conveyances throughout six WHO regions, resulting in 890,392 deaths, giving a tentative 3.3% case fatality rate [225].\nAnalysis of whole-genome sequences showed that SARS-CoV-2 shares about 96.1% identity to a bat SARSr-CoV isolated from Rhinolophus affinis (Ra) in Yunnan, China in 2013 (BatCoV RaTG13) [132,133], 93.3% identity to a bat SARSr-CoV isolated from Rhinolophus malayanus (Rm) in Yunnan (YN), China in 2019 (BetaCoV/Rm/Yunnan/YN02/2019, RmYN02) [133], and 87.8% and 87.6% identity to two bat SARSr-CoVs, BatCoV RpZC45 and BatCoV RpZXC21, respectively, detected in Rhinolophus pusillus (Rp) bats from Zhoushan City (ZXC or ZC), Zhejiang Province, China in 2015 [226]. As was the case for SARS-CoV, SARS-CoV-2 is likely to have originated from Chinese horseshoe bats in the genus Rhinolophus. Although there is high sequence identity between the longest encoding gene region (1ab) of RmYN02 and 1ab of SARS-CoV-2 (nt 97.2%, aa 98.8%), there is low sequence identity between the SARS-CoV-2 S RBD and RaTG13 S RBD (nt 85.3%, aa 89.3%) or RmYN02 S RBD (nt 61.3%, aa 62.4%) [133]. The RBD is a major determinant of host range and it is therefore likely that there is an intermediate host facilitating a bat SARSr-CoV to acquire efficient ability to infect humans.\nAlthough the first outbreak occurred in Wuhan, animal specimens from the Huanan seafood wholesale market in Wuhan, which sells both live and dead animals including bats, civets, snakes, poultry, pigs and dogs, were negative for SARSr-CoVs [226]. Snakes and canids (dogs) were presumed to be intermediate hosts of SARS-CoV-2 based on sequence analysis of the relative synonymous codon usage (RSCU) bias between SARS-CoV-2 and animal host species [227] and based on analysis of zinc finger antiviral protein (ZAP) expression in animal host species and tissues that drive CoV evolution to have a low-CpG (5′-Cytosin-phosphate-Guanine-3′) viral genome [228], respectively. However, SARSr-CoV-2 has not been isolated from snakes and it is unlikely that the viruses can cross the species barrier from bats, warm-blooded mammals, to humans via snakes, cold-blooded reptiles. Although results of RT-PCR and serological tests confirmed SARS-CoV-2 infections in dogs, the infected dogs were with infected owners and thus humans are likely to have transferred the virus to their pets [101]. Cats, tigers and lions that were cared for by infected owners/zookeepers were also reported to have tested seropositive for SARS-CoV-2, suggesting human-to-animal transmission of COVID-19 [101]. Experimental studies showed that pigs, chickens and ducks were not susceptible to SARS-CoV-2, that dogs had little susceptibility and that both ferrets and cats were highly susceptible [229,230]. Experimental studies showed that there is little transmission of SARS-CoV-2 among ferrets but that cats have the potential for airborne transmission of the virus between them [230]. However, no cat-SARSr-CoV-2 has been isolated. Furthermore, there has so far been no evidence of transmission of SARS-CoV-2 or SARSr-CoV-2 from these SARS-CoV-2-susceptible animals, including canines, ferrets and felines, to humans [101,229]. Nonetheless, surveillance of both infection and dissemination of SARS-CoV-2 should be implemented. SARSr-CoV-2 has been isolated from smuggled Malayan pangolins (Manis javanica), but it has not been isolated from Chinese pangolins (Manis pentadactyla) seized in Guangxi (GX) and Guangdong (GD) in southern China [103,226,231]. Whole-genome comparison indicated that pangolin-SARSr-CoVs have a significant sequence difference from SARS-CoV-2 sequences, suggesting that current pangolin-SARSr-CoV isolates are unlikely to be the virus directly transmitted to cause SARS-CoV-2 outbreaks in humans. However, all of the studies [103,133,226,231] showed high aa sequence identities (97.4%) between pangolin SARSr-CoV (pangolin/GD/2019 with a single consensus sequence merged from the GD/P1L and GD/P2S sequences) S RBD and SARS-CoV-2 S RBD. Thus, SARSr-CoV from Malayan pangolins may be able to infect humans or may provide an RBD gene region to a coinfected CoV. Malayan pangolins may serve as a vessel to generate a CoV with human receptor-binding potential due to the high aa sequence similarity between pangolin and human ACE2 receptors (84.8%) [231], suggesting the need for pangolin surveillance for public health. The continued search for a SARS-CoV-2 intermediate host is essential for understanding the emergence of the COVID-19 pandemic and for future prevention and control of zoonotic CoV-related 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