COVID-19 is an infectious disease caused by the coronavirus (SARS-CoV-2), which mainly causes symptoms such as fever and cough. It spreads through droplet transmission or contact transmission. Since 2019, COVID-19 has spread across the world, seriously damaging human health and hindering the development of the global economy. Although vaccination is underway, humans still suffer from the harm caused by COVID-19. Currently, researchers are actively developing oral drugs for COVID-19.

RdRp (RNA-dependent RNA polymerase) is a potential drug target for SARS-CoV-2. RdRp, a key viral enzyme, is critical in mediating viral replication and transcription. The RdRp of SARS-CoV-2 differs from the RdRp of SARS-CoV and MERS-COV27. But the RdRps of all three coronaviruses are highly conserved. Thus, RdRp is a promising broad-spectrum antiviral target for coronaviruses. As an RdRp inhibitor, EIDD-2749 is a promising drug candidate for oral therapy for COVID-19.

EIDD-2749 is an orally active, low cytotoxic, and broad-spectrum RdRp inhibitor.

From: Abas AH, Tallei TE, Fatimawali F et al. F1000Research 2022, 11:410

In vitro studies have shown that EIDD-2749 (4′-Fluorouridine) can effectively block the replication of the respiratory syncytial virus (RSV) and RNA viruses (including SARS-CoV-2). EIDD-2749 also exhibits antiviral activity against the hepatitis C virus and lymphocytic choriomeningitis virus.

In addition, EIDD-2749 (0.2, 1, 5 mg/kg; p.o., single daily for 4 days) shows highly efficacious in the RSV infection mice model. More exciting, an in vivo study reveals that SARS-CoV-2 is highly susceptible to EIDD-2749. The results show that the single daily administration of EIDD-2749 is more effective than the twice daily administration of Molnupiravir.

In conclusion, EIDD-2749 is a broad-spectrum orally active RdRp inhibitor, has potential against major RNA viruses, and becomes a promising therapeutic option for RSV disease and COVID-19.

References：

[1] Sourimant J, et al. Science. 2022 Jan 14;375(6577):161-167. 

[2] Abas AH, et al. F1000Research 2022, 11:410.