Abstract
Knowledge about coronaviruses (CoVs) with furin cleavage sites is extremely limited, although these sites mediate the hydrolysis of glycoproteins in plasma membranes required for MERS-CoV or SARS-CoV-2 to enter cells and infect humans. Thus, we have examined the global epidemiology and evolutionary history of SARS-CoV-2 and 248 other CoVs with 86 diversified furin cleavage sites that have been detected in 24 animal hosts in 28 countries since 1954. Besides MERS-CoV and SARS-CoV-2, two of five other CoVs known to infect humans (HCoV-OC43 and HCoV-HKU1) also have furin cleavage sites. In addition, human enteric coronavirus (HECV-4408) has a furin cleavage site and has been detected in humans (first in Germany in 1988), probably via spillover events from bovine sources. In conclusion, the presence of furin cleavage sites might explain the polytropic nature of SARS-CoV-2- and SARS-CoV-2-like CoVs, which would be helpful for ending the COVID-19 pandemic and preventing outbreaks of novel CoVs.
Highlights
State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming, China
The presence of furin cleavage sites might explain the polytropic nature of SARS-CoV-2- and SARS-CoV-2-like CoVs, which would be helpful for ending the COVID-19 pandemic and preventing outbreaks of novel CoVs
Thorough structural understanding of SARS-CoV-2 is crucial to control the global outbreak of the virus and prevent outbreaks of related viruses
Summary
State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming, China. Furin inhibitors could be potent therapeutic agents for treating SARS-COV-2 infection (Cheng et al, 2020), so it is crucial to obtain detailed knowledge of CoVs with furin cleavage sites to end the COVID-19 pandemic and prevent new potential outbreaks of pathogenic CoVs. To assist such efforts, we retrieved S protein sequences of 2,297 coronaviruses of four genera (Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus) from the National Genomics Data Center (National Genomics Data Center Members and Partners, 2020; see Supplementary Materials).
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