2019-nCoV has become a public health emergency of international concern, and there is a lack of effective treatment strategies for the pneumonia caused by this novel coronavirus. Professor Jingyue Ju’s research team of Chinese scientists has joined the effort to find therapies against 2019-nCoV.
On January 31, their study published on bioRxiv indicated that, due to the similar viral gene replication mechanisms employed by the hepatitis C virus and coronaviruses, it was inferred that the hepatitis C medication Epclusa should also be capable of inhibiting 2019-nCoV [1].
Image source: bioRxiv [1]
Epclusa is a fixed-dose combination of sofosbuvir, an NS5B polymerase inhibitor, and velpatasvir, an NS5A inhibitor. The combination was approved by the FDA and EMA in 2016 and received marketing approval in China in 2018. According to Gilead Sciences’ financial reports, Epclusa’s sales in 2018 approached $2 billion.
In this study, to develop broad-spectrum antiviral drugs, Professor Jingyue Ju’s team conceived a novel strategy for designing and synthesizing viral polymerase inhibitors: combining the ProTide prodrug strategy used in the development of Sofosbuvir with the incorporation of 3’-blocking groups.
The team’s previous research incorporated 3’-blocking groups into nucleoside analogs, enabling them to function as polymerase inhibitors. They posited that these modified nucleoside analogs would serve as effective polymerase inhibitors against various viral diseases, including coronaviruses such as 2019-nCoV, as well as the viruses responsible for SARS and MERS.
Once incorporated with a 3'-blocking group, the newly designed nucleotide analogs will permanently halt further viral gene replication. This contrasts with other nucleoside analog-based viral inhibitors, which possess a free 3'-OH group and may fail to inhibit the polymerase following viral mutations.
Professor Jingyue Ju stated, “We are very hopeful that this approach will work and are eager to share information with colleagues around the world to help address this global emergency.”
Relevant Papers:
[1] Jingyue Ju et al. Nucleotide Analogues as Inhibitors of Viral Polymerases, bioRxiv (2020). DOI: 10.1101/2020.01.30.927574
References:
1# Study shows that hepatitis C drug EPCLUSA has the potential to inhibit coronaviruses (Source: Medical Press)