Repurposing Clinically Approved Drugs for COVID-19: A Breakthrough Using a Pangolin Coronavirus Model

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Repurposing Clinically Approved Drugs for COVID-19: A Breakthrough Using a Pangolin Coronavirus Model

During the COVID-19 pandemic, finding safe, effective treatments for 2019-novel coronavirus (2019-nCoV) infection was a global emergency. But studying live 2019-nCoV requires high-level biosafety labs—something many researchers don’t have access to. A 2020 study from the Beijing University of Chemical Technology offered a clever solution: using a related coronavirus from pangolins to test existing drugs, speeding up the search for potential therapies.

The Pangolin Coronavirus: A Safe, Similar Model

The team focused on a pangolin coronavirus called GX_P2V, isolated in 2017 from a smuggled pangolin in southern China. This virus is remarkably similar to 2019-nCoV: its spike protein (the part that lets viruses enter cells) shares 92.2% of the same amino acids as the Wuhan-hu-1 2019-nCoV isolate. Even more importantly, GX_P2V uses the same cell receptor as 2019-nCoV: angiotensin-converting enzyme 2 (ACE2).

To confirm this, the researchers used small interfering RNA (siRNA)—a tool that “turns off” specific genes—to reduce ACE2 levels in cells. When ACE2 was knocked down, viral infection dropped too. And unlike 2019-nCoV, GX_P2V is non-pathogenic to humans (no cases of human infection were linked to it), so it can be studied in standard biosafety level 2 (BSL-2) labs—far more accessible than the BSL-3/4 facilities needed for live 2019-nCoV.

How They Tested Drugs: Screening 2,406 Approved Compounds

The team’s goal was to find repurposed drugs—already-approved medications that could be repurposed to fight 2019-nCoV. They screened 2,406 clinically approved drugs and anti-viral compounds using GX_P2V and Vero E6 cells (a common lab cell line for virus research).

Each drug was tested at 10 μmol/L (a safe concentration for cells). The team looked for two key things:

  1. Inhibition of cytopathic effect (CPE): Damage to cells caused by the virus (a sign of infection).
  2. Reduced viral load: Lower levels of viral RNA (to track replication) and fewer infectious particles (measured via plaque assays).

The Results: Three Drugs Stopped the Virus—Cepharanthine Was Best

Three drugs completely blocked CPE at 10 μmol/L:

  1. Cepharanthine (CEP): A plant alkaloid approved for leukopenia (low white blood cells).
  2. Selamectin: A topical parasiticide for cats/dogs (kills fleas, heartworms).
  3. Mefloquine hydrochloride: A malaria drug.

But cepharanthine stood out as the most potent:

  • It inhibited 50% of viral infection at just 0.98 μmol/L (a very low, safe dose).
  • At 10 μmol/L, viral RNA levels in treated cells were 15,393 times lower than in untreated cells at 72 hours post-infection.
  • No live virus was found in the media of cepharanthine-treated cells at 48 hours.

The team also uncovered how cepharanthine works: it blocks the virus at two stages—stopping it from entering cells and halting its replication once inside.

Why Cepharanthine Is a Promising Candidate

Cepharanthine isn’t new—and that’s a good thing. It has:

  • Decades of clinical use: Humans have taken it for over 40 years with no major side effects.
  • Low toxicity: It’s safe in animals and humans at therapeutic doses.
  • Proven anti-viral activity: Previous studies show it inhibits other coronaviruses (SARS-CoV, HCoV-OC43) and HIV-1.
  • Anti-inflammatory effects: COVID-19 severity often stems from overactive inflammation—cepharanthine’s ability to calm this response is an extra bonus.

What About the Other Drugs?

  • Selamectin: A first-time find for coronaviruses. It’s used in pets to kill parasites, but its anti-viral mechanism is unknown (the team suspects it targets the virus directly).
  • Mefloquine: Already known to fight MERS-CoV and SARS-CoV. Like cepharanthine, it may target host cell pathways that viruses need to replicate.

Why This Study Matters

This research solves two big problems:

  1. Accessibility: The GX_P2V model lets scientists study coronavirus biology and test drugs without high-level biosafety labs.
  2. Speed: Repurposing approved drugs skips years of safety testing—critical during a pandemic.

While these results are from cell culture (not humans), they’re a crucial first step. Cepharanthine, in particular, checks many boxes: it’s safe, effective in lab tests, and has a proven track record. The team now urges further research—including clinical trials—to confirm if it works in humans.

The Original Study

This research was published in the Chinese Medical Journal in 2020 by a team from the Beijing Advanced Innovation Center for Soft Matter Science and Engineering and the College of Life Science and Technology at Beijing University of Chemical Technology.

Citation: Fan HH, Wang LQ, Liu WL, et al. Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus-related coronavirus model. Chinese Medical Journal 2020;133:1051–1056. doi: doi.org/10.1097/CM9.0000000000000797

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