A review of potential suggested drugs for coronavirus disease (COVID-19) treatment

Abstract

The latest pandemic, coronavirus disease-2019 (COVID-19), is associated with high prevalence and easy transmission, which is expanding globally with no conventional treatment or vaccine. The new virus revealed 79% and 50% genomic similarities with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Accordingly, since the disease resists testing and adopting new therapeutics, repositioning pre-existing drugs may present a fast and attractive strategy with known safety, characteristics, and dosage used. However, they are not specific and targeted. Therefore, several drugs have been investigated for their efficacy and safety in the treatment of COVID-19; most of them are undergoing clinical trials. This article summarizes clinical investigations of potential therapeutic drugs used as COVID-19 therapy. Subsequently, it prepares a pattern of results and therapeutic targets to help further experiment designs. We have investigated drugs as classified in the following three groups; 1) The drugs which computationally showed effectiveness (in silico) but needed further lab confirmations; 2) Emetine, Teicoplanin, and Nelfinavir have shown effectiveness in vitro; 3) The drugs currently under clinical trial.

Keywords: 2019-nCoV; COVID-19; Drug repositioning; Outbreak; Review; SARS-CoV-2.

Fig. 1

The infection cycle of SARS-COV-2 and the effecting pints of potential drugs against COVID-19.1) SARS-COV-2 binds to the cell surface through ACE-II and TMPRSS2 cell membrane proteins (Entrance blocking drugs). 2) Virus enters to the cells through receptor mediated endocytosis and formation of endosomes, 3) Fusion of virus to endosomes leads to the genome releasing to the cytoplasm (Endosome fusion blocking agents), 4) Replication of the genome (Replication inhibitors), 5) Transcription of viral genes, 6) Translation of virus proteins (Virus proteins inhibitors), 7) Packaging the virus particles and, 8) releasing the newly formed virus particles to the extracellular environment. Cytokine storm and inflammatory mediators in the infection site leads to tissue damage (Inhibitors of inflammatory mediators). Clot formation, as a secondary effect of COVID-19, is inhibited by heparins. Bradykinin receptor repressor inhibits plasma leakage to the lung tissue. BK: Bradykinin, ACE-II angiotensin converting enzyme 2, IFN: Interferon, IL-6: Interleukin 6, IL-1, Interleukin 1, TNFa: Tumor necrosis factor α, EGFR: Epidermal growth factor receptor, TMPRSS2: Transmembrane serine protease 2.