SARS-CoV-2 Exoribonuclease (NSP14) As a Potential Therapeutic Target to Treat COVID-19

17 Pages Posted: 26 Jun 2020

See all articles by Adrián Cruz-González

Adrián Cruz-González

Universidad Nacional Autonoma de Mexico

Abelardo Aguilar-Cámara

Universidad Nacional Autónoma de México

Claudia Álvarez-Carreño

Universidad Nacional Autonoma de Mexico

Arturo Becerra

Universidad Nacional Autonoma de Mexico

José Alberto Campillo-Balderas

Universidad Nacional Autonoma de Mexico

Alejandro Cisneros-Martínez

Universidad Nacional Autonoma de Mexico

Grisel Córdova-Villalba

Universidad Nacional Autonoma de Mexico

Wolfgang Cottom-Salas

Universidad Nacional Autonoma de Mexico

Coral Cruz-González

Universidad Nacional Autonoma de Mexico

Ricardo Hernández-Morales

UNAM

Ingrid Miranda-Pérez

Universidad Nacional Autonoma de Mexico

Israel Muñoz-Velasco

Universidad Nacional Autonoma de Mexico; National Autonomous University of Mexico (UNAM)

Luis Alonso Quintero-Navarro

Universidad Nacional Autonoma de Mexico

Mario Rivas

University of Houston

Noel Cabañas

Universidad Nacional Autonoma de Mexico

Alma Carolina Sánchez-Rocha

Charles University

Alberto Vázquez-Salazar

University of California, Los Angeles (UCLA)

Rodrigo Jácome

Universidad Nacional Autonoma de Mexico

Antonio Lazcano

Universidad Nacional Autonoma de Mexico

Date Written: June 18, 2020

Abstract

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

Cruz-González, Adrián and Aguilar-Cámara, Abelardo and Álvarez-Carreño, Claudia and Becerra, Arturo and Campillo-Balderas, José Alberto and Cisneros-Martínez, Alejandro and Córdova-Villalba, Grisel and Cottom-Salas, Wolfgang and Cruz-González, Coral and Hernández-Morales, Ricardo and Miranda-Pérez, Ingrid and Muñoz-Velasco, Israel and Quintero-Navarro, Luis Alonso and Rivas, Mario and Cabañas, Noel and Sánchez-Rocha, Alma Carolina and Vázquez-Salazar, Alberto and Jácome, Rodrigo and Lazcano, Antonio, SARS-CoV-2 Exoribonuclease (NSP14) As a Potential Therapeutic Target to Treat COVID-19 (June 18, 2020). Available at SSRN: https://ssrn.com/abstract=3632018

Adrián Cruz-González

Universidad Nacional Autonoma de Mexico ( email )

Av Universidad 3000
Apdo. Postal 70-407
Mexico City, Mexico City 04510
Mexico

Abelardo Aguilar-Cámara

Universidad Nacional Autónoma de México ( email )

México

Claudia Álvarez-Carreño

Universidad Nacional Autonoma de Mexico ( email )

Alcanfores y San Juan Totoltepec s/n Santa Cruz Ac
Naucalpan, Estado de México 53150
Mexico

Arturo Becerra

Universidad Nacional Autonoma de Mexico ( email )

Alcanfores y San Juan Totoltepec s/n Santa Cruz Ac
Naucalpan, Estado de México 53150
Mexico

José Alberto Campillo-Balderas

Universidad Nacional Autonoma de Mexico ( email )

Apdo. Postal 70-407, Av Universidad 3000
Ciudad Universitaria, Coyoacán
Mexico City, Mexico City 04510
Mexico

Alejandro Cisneros-Martínez

Universidad Nacional Autonoma de Mexico ( email )

Av. Universidad 3000
Mexico City, Estado de México 70-407
Mexico

Grisel Córdova-Villalba

Universidad Nacional Autonoma de Mexico ( email )

Alcanfores y San Juan Totoltepec s/n Santa Cruz Ac
Naucalpan, Estado de México 53150
Mexico

Wolfgang Cottom-Salas

Universidad Nacional Autonoma de Mexico ( email )

Av. Universidad 3000
Mexico City, Estado de México 70-407
Mexico

Coral Cruz-González

Universidad Nacional Autonoma de Mexico ( email )

Alcanfores y San Juan Totoltepec s/n Santa Cruz Ac
Naucalpan, Estado de México 53150
Mexico

Ricardo Hernández-Morales

UNAM ( email )

Av. Universidad 3000
Mexico city, CDMX 04510
Mexico

Ingrid Miranda-Pérez

Universidad Nacional Autonoma de Mexico ( email )

Alcanfores y San Juan Totoltepec s/n Santa Cruz Ac
Naucalpan, Estado de México 53150
Mexico

Israel Muñoz-Velasco

Universidad Nacional Autonoma de Mexico

Av. Universidad 3000
Mexico City
Mexico

National Autonomous University of Mexico (UNAM) ( email )

Av. Universidad 3000
Mexico City
Mexico

Luis Alonso Quintero-Navarro

Universidad Nacional Autonoma de Mexico ( email )

Alcanfores y San Juan Totoltepec s/n Santa Cruz Ac
Naucalpan, Estado de México 53150
Mexico

Mario Rivas

University of Houston ( email )

4800 Calhoun Road
Houston, TX 77204
United States

Noel Cabañas

Universidad Nacional Autonoma de Mexico ( email )

Av.Universidad 3000
Ciudad de México, Ciudad de México 53150
Mexico

Alma Carolina Sánchez-Rocha

Charles University ( email )

U Knize 8
Prague, 15800
Czech Republic

Alberto Vázquez-Salazar

University of California, Los Angeles (UCLA) ( email )

420 Westwood Plaza
Boelter Hall
Los Angeles, CA 90095
United States

Rodrigo Jácome

Universidad Nacional Autonoma de Mexico ( email )

Alcanfores y San Juan Totoltepec s/n Santa Cruz Ac
Naucalpan, Estado de México 53150
Mexico

Antonio Lazcano (Contact Author)

Universidad Nacional Autonoma de Mexico ( email )

Alcanfores y San Juan Totoltepec s/n Santa Cruz Ac
Naucalpan, Estado de México 53150
Mexico

Here is the Coronavirus
related research on SSRN

Paper statistics

Downloads
99
Abstract Views
447
rank
290,958
PlumX Metrics