Preliminary Study on Resistance of Coxsackievirus A10 to Ribavirin
In recent years,the infection rate of hand,foot,and mouth disease(HFMD)has gradually increased nationwide,with Coxsackievirus A10(CVA10)being one of the main pathogens.Ribavirin is one of the commonly used drugs for treatment of HFMD in children.In order to evaluate the clinical efficacy of ribavirin in the treatment of CVA10 infection,in this study,we randomly selected 19 representative CVA10 strains with dominant genotype C in mainland of China from 2009 to 2021 in different regions and different years,and detected the inhibition rate of ribavirin on CVA10 in RD cells through cell counting kit-8(CCK8).CVA10 strains with inhibition rate greater than 85％was defined as sensitive group to ribavirin,while CVA10 with inhibition rate less than 15％was defined as resistant group to ribavirin.The results showed that ribavirin had a good inhibitory effect on CVA10 at a concentration of 0.78mmol/L and had low cytotoxicity to RD cells.Among the 19 CVA10 strains,four showed resistance to ribavirin,two showed sensitive to ribavirin,and the remaining thirteen showed sensitivity between 85％and 15％.The pathogenicity of the sensitive and resistant strains to ribavirin was compared in 7-day-old sucking mice infection experiments.The clinical scores,survival rate,body weight and viral titer measurements of tissue samples in suckling mice showed that the pathogenicity of the sensitive group CVA10 was stronger than that of the resistant group.Furthermore,the MEGA 7.0 software was used to perform differential analysis on the 2C region amino acid sequences that affect CVA10 replication and translation,in order to identify potential drug resistance sites.The results showed differences in the amino acid sites at positions 327 and 328 in the 2C region of CVA10 between the ribavirin-resistant group and the sensitive group.This study showed that the currently circulating CVA10 strains in China is widely resistance to ribavirin,with some CVA10 strains being completely resistant.Therefore,it is necessary to strengthen the monitoring of CVA10 resistant strains in order to better guide clinical doctors in selecting antiviral drugs correctly and provide theoretical basis for personalized treatment.
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