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Published on: November 5, 2021
Anti-SARS-CoV-2 prodrug ATV006 has broad-spectrum antiviral activity against human and animal coronaviruses
Tiefeng Xu1, Kun Li2, Siyao Huang1
1Centre for Infection and Immunity Studies (CIIS), School of Medicine, Shenzhen Campus of Sun Yat-sen University, Guangzhou 518107, China.
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.
Insights
A new drug, ATV006, shows broad antiviral effects against multiple coronaviruses, including SARS-CoV-2. This nucleoside analog is effective even when given late, offering potential for treating diverse coronavirus infections in humans and animals.
Area of Science:
- Virology
- Drug Discovery
- Infectious Diseases
Background:
- Coronavirus diseases present a global health challenge, exacerbated by viral diversity and unpredictable outbreaks.
- The "one bug, one drug" approach is insufficient for emerging coronavirus threats.
- Broad-spectrum antiviral agents are critically needed to combat diverse coronavirus infections.
Purpose of the Study:
- To evaluate the broad-spectrum antiviral activity of ATV006, a nucleoside analog targeting RNA-dependent RNA polymerase (RdRp).
- To assess ATV006's efficacy against both human and animal coronaviruses.
Main Methods:
- Utilized mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as model systems.
- Administered ATV006 to mice to evaluate prophylactic and therapeutic effects against murine coronavirus infection in vivo.
- Tested ATV006 efficacy at various time points post-infection, including a delayed administration at 96 hours.
Main Results:
- ATV006 demonstrated potent prophylactic and therapeutic antiviral activity against MHV infection in mice.
- The drug effectively inhibited viral replication even when administered 96 hours after infection.
- ATV006 exhibits broad antiviral activity across different coronavirus strains.
Conclusions:
- ATV006, an RdRp-targeting nucleoside analog, possesses broad-spectrum anti-coronavirus efficacy.
- Its oral bioavailability and potent activity against multiple coronaviruses position it as a promising therapeutic candidate.
- ATV006 holds potential for treating SARS-CoV-2 and other emerging or circulating human and animal coronavirus infections.
