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Antiviral Therapy Update: SARS-CoV-2 RdRp is a versatile enzyme with proofreading activity and ability to incorporate NHC into RNA

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eMediNexus    08 February 2022

The coronavirus disease 2019 (COVID-19) has been for almost two years and has severely impaired both human health and the economy. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilises the viral RNA-dependent RNA polymerase (RdRp) complex for genome replication and transcription, making it an attractive focus for antiviral drug development. 

The structure of the RdRp complex has been specified, but its function still needs to be fully characterized. A study described that along with RNA dependent RNA polymerase activity, RdRp also conducts exoribonuclease activity and accordingly proofreading activity. RdRp and nsp14-ExoN, when united, display higher proofreading activity than RdRp alone. Furthermore, RdRp identifies and employ nucleoside diphosphate (NDP) as a substrate to synthesize RNA and also include β-d-N4-hydroxycytidine (NHC) into RNA while using diphosphate form molnupiravir as substrate.

SOURCE- bioRxiv 2021.11.15.468737; doi: https://doi.org/10.1101/2021.11.15.468737

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