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Mutation and Virulence of SARS-CoV-2 Strains Circulating in Anhui Province, China

Background: The genome of SARS-CoV-2 has shown considerable variation during its spreading. Monitoring variations in the virus genome to understand the evolution and spread of the virus is extremely important.  
 
Methods: Seven SARS-CoV-2 strains (BB127, BB183, HB030, MAS525, HF3028, FY1494, and SZ005) circulating in Anhui Province, China were isolated and sequenced for evolutionary analysis. Five strains were further cultured in vitro and were subjected to viral growth assay, TCID50 assay, and detection of spike protein expression. Next generation sequence (NGS) analysis were applied to investigate the mutation frequencies throughout the whole genome at different time gradients in vitro.  
 
Findings: Our observations revealed that in vitro cultured SARS-CoV-2 virus had much higher mutation frequency (up to ~20 times) than that in infected patients, and the mutation in nonstructural protein 14 (nsp14) might increase the genomic mutation frequency. Different strains had various amount of spike protein which may positively correlated with the virus replication capacity but may be influenced by other viral factors.  
 
Interpretation: Our study suggested that SARS-CoV-2 has the potential to diversify under favorable conditions. Monitoring viral mutations is not only helpful for better understanding of virus evolution and virulence change, but also the key to prevent virus transmission and disease progression. SARS-CoV-2 genomic variation analysis may also provide potential ideas for more efficient vaccine development and clinical treatment.  
 
Funding: This work is funded by Special Project for Emergency Scientific and Technological Research on New Coronavirus Infection (YG, No. YD9110002001), Emergency Research Project of Novel Coronavirus Infection of Anhui Province (Grant numbers 202004a07020002; 202004a07020004), Postdoctoral Research Foundation of China (2020M670084ZX) and the Fundamental Research Funds for the Central Universities (WK9110000166; WK9110000167). 
 
Declaration of Interests: We declare no competing interests. 
 
Ethics Approval Statement: The study was conformed to the principles of the Declaration of 
Helsinki and approved by the Ethics Committee of the First Affiliated Hospital of USTC..