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Probable pangolin origin of SARS-CoV-2 associated with the COVID-19 outbreak

Our take —

Reanalysis of sequences from Malayan pangolins seized in Guangdong reveals a SARS-CoV-2-related coronavirus. The pangolin coronavirus is less similar to SARS-CoV-2 than bat coronavirus RaTG13 across the whole genome, but is more similar within the spike protein. The similarity of bat and pangolin viruses is still insufficient to implicate pangolins as intermediate hosts responsible for spillover to humans; more sampling is necessary to ascertain the exact zoonotic origin of SARS-CoV-2.

Study design

Ecological

Study population and setting

Reinvestigation of sequencing data from Liu et al. (https://doi.org/10.3390/v11110979). In that study, organ samples (lung, lymph, spleen) were collected from dead Malayan pangolins at the Guangdong Wildlife Rescue Center, Guangdong, southern China. The samples were derived from 21 live Malayan pangolins seized by the Anti-smuggling Customs Bureau on March 24, 2019; the animals were in poor condition and 16 died in captivity, the majority of which showing swollen lungs containing frothy liquid. A total of 21 organ samples from 11 dead pangolins that had shown symptoms were chosen for sequencing analysis.

Summary of Main Findings

Coronavirus sequences from two lung samples showed low similarity (80-89%) in their genetic code to SARS coronavirus and related viruses in bats. Upon revised phylogenetic analysis comparing the genetic code of SARS-CoV-2 and related bat coronaviruses, the virus found in pangolins is included as part of the SARS-CoV-2-related coronaviruses. Similar to the results from Lam et al. (https://doi.org/10.1038/s41586-020-2169-0), a coronavirus from an insectivorous bat in China (RaTG13) was shown to be most closely related to SARS-CoV-2 on average across the whole genome. However, the Guangdong pangolin virus was more closely related than RaTG13 to SARS-CoV-2 within the region of the genome that codes for the spike protein, which SARS-CoV-2 uses to bind and enter human cells. Additionally, the region between the two subunits of the spike protein contains a unique insertion of amino acids that is not present an any of the SARS-CoV-2-related genomes from bats or pangolins, although similar insertions have been found in MERS-CoV.

Study Strengths

The study capitalizes on existing sequencing data to rapidly identify the phylogenetic relatedness between pangolin coronaviruses and SARS-CoV-2. Within the original study by Liu et al., the sequencing approach they used is a powerful method for detecting diverse viral infections in symptomatic animals.

Limitations

Sequencing alone is not sufficient to establish that the detected coronavirus was the cause of symptoms or mortality in the sampled animals. Similar to the study by Lam et al., the similarity between the pangolin coronaviruses and SARS-CoV-2 is not high enough to implicate pangolins as intermediate hosts of SARS-CoV-2. The trafficked animals were likely from Southeast Asia and were collected in Guangdong, which is very distant from the original outbreak in Wuhan. More sampling of animals, especially in and around Wuhan, is necessary to reveal coronaviruses that are even more closely related to SARS-CoV-2.

Value added

This study provides additional information supporting a natural, zoonotic origin of SARS-CoV-2.