Introduces of COVID-19 and Darunavir ethanolate

COVID-19 is a disease that is caused by the novel coronavirus known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Angiostensin converter (ACE2) enzymes are used as receptors by SARS-CoV, SARS-CoV-2, and HCoV-NL63.

Darunavir ethanolate: the drug approved for the treatment of HIV and used in the combination with cobicistat to inhibit the viral main protease. Darunavir is considered for combating the resistance to standard HIV therapy as a second generation protease inhibitor and it is generally used in combination with cobicistat to produce more therapeutic effectiveness. It has been assumed that it can also inhibit the protease of the SARS-CoV-2. Darunavir is being studied as a probable treatment for SARS-CoV-2, because of its in vitro results supporting its potency to eradicate this infection. Some clinical trials are on-going and are predicted to conclude soon.

Drug repurposing

Drug repurposing, also known as drug repositioning or drug re-profiling, works as an alternate, systematic method in drug discovery that can aid in determining the new indications for the existing drugs.

Molecular docking

The binding energies of Darunavir ethanolate and SARS-CoV-2 were -7.8 kcal/mol which is superior to the co-crystallised ligand (-7 kcal/mol). This result provides one more evidence that darunavir ethanolate can be the potential inhibitor of the SARS-CoV-2 protease.

Adverse events

So far, no major adverse events have been observed with darunavir, but mild diarrhoea and renal insufficiency have been observed in patients treated with darunavir/cobicistat compared to standard therapy. There is an increased risk of myocardial infarction in HIV patients treated with darunavir. In addition, it should be used with caution in patients with underlying heart problems.

References：
[1] CHAVDAVIVEK P. Darunavir ethanolate: Repurposing an anti-HIV drug in COVID-19 treatment.[J]. European Journal of Medicinal Chemistry Reports, 2021, 3: 100013. DOI:10.1016/j.ejmcr.2021.100013. 

[2] SANG P, TIAN S H, MENG Z H, et al. Anti-HIV drug repurposing against SARS-CoV-2?[J]. RSC Advances, 2020, 27: 15775-15783. DOI:10.1039/D0RA01899F.

[3] KAWTHAR MOHAMED . Computational drug discovery and repurposing for the treatment of COVID-19: A systematic review[J]. Bioorganic Chemistry, 2021, 106: Article 104490. DOI:10.1016/j.bioorg.2020.104490.