The multiple roles of viral 3D^pol protein in picornavirus infections

ABSTRACT

The Picornaviridae are a large group of positive-sense, single-stranded RNA viruses, and most research has focused on the Enterovirus genus, given they present a severe health risk to humans. Other picornaviruses, such as foot-and-mouth disease virus (FMDV) and senecavirus A (SVA), affect agricultural production with high animal mortality to cause huge economic losses. The 3D^pol protein of picornaviruses is widely known to be used for genome replication; however, a growing number of studies have demonstrated its non-polymerase roles, including modulation of host cell biological processes, viral replication complex assembly and localization, autophagy, and innate immune responses. Currently, there is no effective vaccine to control picornavirus diseases widely, and clinical therapeutic strategies have limited efficiency in combating infections. Many efforts have been made to develop different types of drugs to prohibit virus survival; the most important target for drug development is the virus polymerase, a necessary element for virus replication. For picornaviruses, there are also active efforts in targeted 3D^pol drug development. This paper reviews the interaction of 3D^pol proteins with the host and the progress of drug development targeting 3D^pol.

KEYWORDS:

• Picornaviruses
• 3D^pol
• RNA-dependent RNA polymerase
• virus-host interaction
• RdRp inhibitor

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

J.P. and H.Z. wrote the initial draft with input from Z.N., F.Z., and H.Z., Z.N., F.Z., H.Z., H.Z., and J.P. edited the final draft.

Availability of data

Data sharing is not applicable to this article as no new data were created or analysed in this study.

Additional information

Funding

We acknowledge support from the National Key R&D Program of China [2021YFD1800300]; the Hatch Project of State Key Laboratory for Animal Disease Control and Prevention [SKLADCP2023HP02]; the Key Project of National Natural Sciences Foundation of China [32330107]; the Science and Technology Major Project of Gansu Province [22ZD6NA001]; and the Innovative Group for Basic Research on the Interaction Between Important Pathogens and Livestock [23JRRA561].