Anti-SARS-CoV-2 prodrug ATV006 has broad-spectrum antiviral activity against human and animal coronaviruses.
10.1016/j.apsb.2025.02.028
- Author:
Tiefeng XU
1
;
Kun LI
2
;
Siyao HUANG
1
;
Konstantin I IVANOV
3
;
Sidi YANG
3
;
Yanxi JI
1
;
Hanwei ZHANG
1
;
Wenbin WU
1
;
Ye HE
4
;
Qiang ZENG
1
;
Feng CONG
5
;
Qifan ZHOU
6
;
Yingjun LI
7
;
Jian PAN
1
;
Jincun ZHAO
3
;
Chunmei LI
1
;
Xumu ZHANG
6
;
Liu CAO
1
;
Deyin GUO
1
Author Information
1. Centre for Infection and Immunity Studies (CIIS), School of Medicine, Shenzhen Campus of Sun Yat-sen University, Guangzhou 518107, China.
2. Institute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of the Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
3. Guangzhou Laboratory, Bio-island, Guangzhou 510320, China.
4. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
5. Guangdong Province Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou 510663, China.
6. Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, Shenzhen Grubbs Institute and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen 518000, China.
7. State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China.
- Publication Type:Journal Article
- Keywords:
Animal coronaviruses;
Antiviral therapy;
Broad-spectrum antiviral activity;
Human coronaviruses;
In vivo;
Oral bioavailability;
RNA-dependent RNA polymerase (RdRp);
SARS-CoV-2
- From:
Acta Pharmaceutica Sinica B
2025;15(5):2498-2510
- CountryChina
- Language:English
-
Abstract:
Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.
