Exploring the natural origins of SARS-CoV-2 in the light of recombination

Abstract

SummaryThe lack of an identifiable intermediate host species for the proximal animal ancestor of SARS-CoV-2 and the distance (~1500 km) from Wuhan to Yunnan province, where the closest evolutionary related coronaviruses circulating in horseshoe bats have been identified, is fueling speculation on the natural origins of SARS-CoV-2. Here we analyse SARS-CoV-2’s related bat and pangolin Sarbecoviruses and confirm horseshoe bats, Rhinolophus, are the likely true reservoir species as their host ranges extend across Central and Southern China, and into Southeast Asia. This would explain the bat Sarbecovirus recombinants in the West and East China, trafficked pangolin infections and bat Sarbecovirus recombinants linked to Southern China, and the recently reported bat Sarbecovirses in Cambodia and Thailand. Some horseshoe bat species, such as R. affinis seem to play a more significant role in virus spread as they have larger ranges. Recent ecological disturbances as a result of changes in meat sources could explain SARS-CoV-2 transmission to humans through direct or indirect contact with infected wildlife, and subsequent emergence towards Hubei in Central China. The only way, however, of finding the animal progenitor of SARS-CoV-2 as well as the whereabouts of its close relatives, very likely capable of posing a similar threat of emergence in the human population and other animals, will be by (carefully) increasing the intensity of our sampling.

Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic

“…All sequences associated with this market differ from RaTG13 by at least three more mutations than sequences subsequently collected at various other locations (Figure 3)-a fact that is difficult to reconcile with the idea that the market was the original location of spread of a bat coronavirus into humans. Importantly, all these observations also hold true if SARS-CoV-2 is compared to other related bat coronaviruses (Lytras et al 2021) such as RpYN06 (Zhou et al 2021) or RmYN02 (Zhou et al 2020a) rather than RaTG13 (Figure S3).…”

“…However, attempts to infer this progenitor have been confounded by a perplexing fact: the earliest reported sequences from Wuhan are not the sequences most similar to SARS-CoV-2's bat coronavirus relatives (Pipes et al 2021). This fact is perplexing because although the proximal origin of SARS-CoV-2 remains unclear (i.e., zoonosis versus lab accident), all reasonable explanations agree that at a deeper level the SARS-CoV-2 genome is derived from bat coronaviruses (Lytras et al 2021). One would therefore expect the first reported SARS-CoV-2 sequences to be the most similar to these bat coronavirus relatives-but this is not the case.…”

“…However, the Wuhan sequences that are available have also confounded phylogenetic analyses designed to infer the "progenitor" of SARS-CoV-2, which is the sequence from which all other currently known sequences are descended (Kumar et al 2021). Although there is debate about exactly how SARS-CoV-2 entered the human population, it is universally accepted that the virus's deep ancestors are bat coronaviruses (Lytras et al 2021). But the earliest known SARS-CoV-2 sequences, which are mostly derived from the Huanan Seafood Market, are notably more different from these bat coronaviruses than other sequences collected at later dates outside Wuhan.…”

How One Pandemic Led To Another: Asfv, the Disruption Contributing To Sars-Cov-2 Emergence in Wuhan

“…Major meat shortages, such as of pork between 2018-2019 in China due to the ASFV epidemic, has significant ecological/socio-economic and epidemiological consequences, which likely contributed to the use of alternative animal sources of meat and in particular increased contact with wildlife. This we hypothesis has indirectly led to the SARS-CoV-2 outbreak in Wuhan, a city in Central China ~1500 Km from Yunnan where its closest evolutionary related horseshoe bat coronavirus was sampled 18 . Note, the divergence of these closest bat Sarbecoviruses from the SARS-CoV-2 progenitor (corresponding to many decades of evolution) indicates the viruses that emerged in Wuhan is not necessarily from Yunnan and that sampling should be widened to other areas horseshoe bat species reside in China.…”

“…Importantly, these provinces (e.g., Guangxi and Guangdong) with much higher pig prices and volatility traditionally consumed much more wildlife than the rest of China 31,32 . Moreover, these provinces overlap with the host range of the four potential hosts of the proximal SARS-CoV-2 ancestor, R.affinis, R.sinicus, R. ferrumequinum and R. malayanus 18 . It is striking that in Yunnan, a major pig producer in Southern China, pig prices stayed among the lowest range, 8-9 Yuan/kg cheaper than the surrounding Sichuan and Guangxi (Figure 2a-f), which were still under the government ASFV restrictions for shipping out pigs and pork products due to two ASFV outbreaks.…”