Strategies for the development of drugs targeting novel coronavirus 2019-nCoV / 药学学报

ABSTRACT

@# There is no specific drug that has been approved for 2019-nCoV. There are a number of factors that pose major challenges in their development. Approaches to the development of anti-2019-nCoV include screening existing broad-spectrum antiviral drugs, repositioning of readily available clinical compounds, and <italic>de novo</italic> development of novel and specific agents for 2019-nCoV. Candidate compounds can be developed either to inhibit virus-based targets, such as RNA proteases, polymerase, spike glycoproteins, and viral envelop and membrane proteins, or to inhibit host-based targets, such as receptors and proteases that are utilized by virus for viral entry and endocytosis. Recently, the RNA polymerase remdesivir had demonstrated clinical efficacy in one patient with severe novel coronavirus pneumonia (NCP). The broad-spectrum viral protease inhibitor Kaletra^® is also recommended in the current NCP clinical practice. Both drugs had lately been proceeded into multiple controlled phase III clinical trials to test their safety and efficacy in NCP. Combinational therapies consisting of multiple drugs provide other viable options against 2019-nCoV, based on scientific and clinical rationales. Using bioinformatics and database analysis, we have identified 75 clinically compounds, including 20 marketed compounds, that are efficacious in inhibiting key targets in virus- and host-based approaches, which may facilitate the development of new therapeutic options for 2019-nCoV.