Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China

F1000Res. 2020 Jan 31:9:72. doi: 10.12688/f1000research.22211.2. eCollection 2020.

Abstract

A novel coronavirus (2019-nCoV) originating in Wuhan, China presents a potential respiratory viral pandemic to the world population. Current efforts are focused on containment and quarantine of infected individuals. Ultimately, the outbreak could be controlled with a protective vaccine to prevent 2019-nCoV infection. While vaccine research should be pursued intensely, there exists today no therapy to treat 2019-nCoV upon infection, despite an urgent need to find options to help these patients and preclude potential death. Herein, I review the potential options to treat 2019-nCoV in patients, with an emphasis on the necessity for speed and timeliness in developing new and effective therapies in this outbreak. I consider the options of drug repurposing, developing neutralizing monoclonal antibody therapy, and an oligonucleotide strategy targeting the viral RNA genome, emphasizing the promise and pitfalls of these approaches. Finally, I advocate for the fastest strategy to develop a treatment now, which could be resistant to any mutations the virus may have in the future. The proposal is a biologic that blocks 2019-nCoV entry using a soluble version of the viral receptor, angiotensin-converting enzyme 2 (ACE2), fused to an immunoglobulin Fc domain, providing a neutralizing antibody with maximal breath to avoid any viral escape, while also helping to recruit the immune system to build lasting immunity. The sequence of the ACE2-Fc protein is provided to investigators, allowing its possible use in recombinant protein expression systems to start producing drug today to treat patients under compassionate use, while formal clinical trials are later undertaken. Such a treatment could help infected patients before a protective vaccine is developed and widely available in the coming months to year(s).

Keywords: 2019-nCoV; ACE2; Wuhan; coronavirus; neutralizing antibody; outbreak.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Antibodies, Monoclonal* / therapeutic use
  • Antibodies, Neutralizing / therapeutic use*
  • Betacoronavirus* / drug effects
  • COVID-19
  • COVID-19 Drug Treatment
  • China / epidemiology
  • Compassionate Use Trials
  • Coronavirus Infections / drug therapy*
  • Disease Outbreaks
  • Drug Repositioning*
  • Humans
  • Oligonucleotides / therapeutic use
  • Peptidyl-Dipeptidase A / drug effects*
  • Pneumonia, Viral / drug therapy*
  • SARS-CoV-2

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Oligonucleotides
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2

Grants and funding

The author(s) declared that no grants were involved in supporting this work.