Characterization of minigenome systems for Hantaan and Seoul hantaviruses

Some rodent-borne hantaviruses are known to cause hemorrhagic fever with renal syndrome in Europe and Asia, and hantavirus cardiopulmonary syndrome in the Americas. Despite the significant public health threat caused by hantaviruses, there are no antiviral therapeutics approved to treat hantavirus infections. One of the major limitations to study these viruses is the requirement for biosafety level 3 (BSL-3) containment. To address this concern, we previously generated a Seoul virus (SEOV) minigenome system which could be used to screen antivirals at BSL-2 level. Here, we report the development of a similar minigenome system based on the L segment of the prototype hantavirus, Hantaan virus (HTNV). In addition, we examined the activity of minigenomes based on M and S segments of SEOV and HTNV. Furthermore, we used the new HTNV minigenome system to confirm the activity of a selected group of antiviral compounds targeting the viral polymerase. All tested compounds (2'-deoxy-2'-Fluorocytidine, baloxavir, remdesivir and ribavirin) show potent anti-HTNV activity. The minigenome systems could be useful tools to study replication mechanisms and to screen antiviral compounds against hantaviruses at lower containment laboratories.