SARS-CoV-2 Exoribonuclease (NSP14) As a Potential Therapeutic Target to Treat COVID-19
17 Pages Posted: 26 Jun 2020
Date Written: June 18, 2020
Although the global health emergency caused by SARS-CoV-2 has led to unprecedented health and socioeconomic crisis, as of today neither an antiviral treatment has been approved for COVID-19, nor is a vaccine available. Like other coronaviruses, SARS-CoV-2 encodes a 3’-5’ exoribonuclease whose proofreading activity contributes to the maintenance of its large genome integrity and stability. The viral exonuclease shares biochemical and structural properties with cellular DnaQ-like exonucleases, suggesting that it was snatched by an ancestral coronavirus. Structural superpositions of the viral exonuclease with its cellular homologs exhibit a remarkable degree of conservation. Accordingly, inhibition mechanisms targeting the catalytic core may block both the cellular and viral exonucleases. Although the SARS-CoV-2 exonuclease has received little attention in the struggle against the COVID-19 pandemic, molecular docking assay suggests that inhibitors of cellular exonucleases may have antiviral activity. Hence, we argue that drug development and testing should consider SARS-CoV-2’s exonuclease as a therapeutic target.
Note: Funding: LAQN, IMV, AAC, GCV, ACM are graduate students at the Universidad Nacional Autónoma de México (UNAM). CAC is supported by a Fulbright García-Robles Fellowship. Financial support from the NIH (DP2 GM123457-01) to AVS is acknowledged. MR’s research was supported by an appointment to the NASA Postdoctoral Program at the NASA Astrobiology Institute, administered by the Universities Space Research Association under contract with NASA.
Conflict of Interest: The authors declare no conflicts of interest.
Keywords: SARS-CoV-2; COVID-19; Exoribonuclease; DnaQ-like exonucleases; Exonuclease; Inhibitors
Suggested Citation: Suggested Citation