Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: An evaluation of the evidence

Abstract

The novel coronavirus infection that initially found at the end of 2019 has attracted great attention. So far, the number of infectious cases has increased globally to more than 100 thousand and the outbreak has been defined as a pandemic situation, but there are still no "specific drug" available. Relevant reports have pointed out the novel coronavirus has 80% homology with SARS. In the difficulty where new synthesized drug cannot be applied immediately to patients, "conventional drug in new use" becomes a feasible solution. The first medication experience of the recovered patients in the US has led remdesivir to be the "specific drug". China has also taken immediate action to put remdesivir into clinical trials with the purpose of applying it into clinical therapeutics for Corona Virus Disease 2019 (COVID-19). We started from the structure, immunogenicity, and pathogenesis of coronavirus infections of the novel coronavirus. Further, we analyzed the pharmacological actions and previous trials of remdesivir to identify the feasibility of conducting experiments on COVID-19.

Keywords: Corona virus disease 2019; Phase III clinical trial; Remdesivir; Severe acute respiratory syndrome coronavirus 2.

Fig. 1

The RNA diagram of SARS-CoV-2 The structure of spike protein is downloaded from RCSB PBD (http://www.rcsb.org/pdb/home/home.do, accessed Feb 25); The model that S protein receptor binding domain (RBD) bind to ACE2 is downloaded from National Microbiology Data Center (http://nmdc.cn/?from=groupmessage&isappinstalled=0#/, accessed Feb 25).

Fig. 2

SARS-CoV-2 invasion process and how remdesivir works 1 SARS-CoV-2 enters target cells by binding the S protein to the ACE2 receptor on the cell surface; 2 Remdeivir, the nucleotide analogues, act as RdRp inhibitors, can provide a scheme for blocking RNA replication; 3Once remdesivir added into the growing chain (i position), is cannot cause an immediate stop. On the contrary, it will continue to extend three more nucleotides down to stop the strand at (i + 3) position; 4 Remdesivir triphosphate cannot be removed by nsp14-ExoN.

Fig. 3

Structure of remdesivir and its precursors and metabolites The original structure of the drug is derived from DRUGBANK (https://www.drugbank.ca, accessed Feb 25).