NIH - HUMAN SYNTHESIS - 02 Oct 2021 (or EPUB)
Background: Severe acute respiratory syndrome (SARS) is caused by a newly discovered coronavirus (SARS-CoV). No effective prophylactic or post-exposure therapy is currently available.
Results: We report, however, that chloroquine has strong antiviral effects on SARS-CoV infection of primate cells. These inhibitory effects are observed when the cells are treated with the drug either before or after exposure to the virus, suggesting both prophylactic and therapeutic advantages. In addition to the well-known functions of chloroquine such as elevations of endosomal pH, the drug appears to interfere with terminal glycosylation of the cellular receptor, angiotensin-converting enzyme 2. This may negatively influence the virus-receptor binding and abrogate the infection, with further ramifications by the elevation of vesicular pH, resulting in the inhibition of infection and spread of SARS CoV at clinically admissible concentrations.
Conclusion: Chloroquine is effective in preventing the spread of SARS CoV in cell culture. Favorable inhibition of virus spread was observed when the cells were either treated with chloroquine prior to or after SARS CoV infection. In addition, the indirect immunofluorescence assay described herein represents a simple and rapid method for screening SARS-CoV antiviral compounds.
Martin J Vincent 1, Eric Bergeron, Suzanne Benjannet, Bobbie R Erickson, Pierre E Rollin, Thomas G Ksiazek, Nabil G Seidah, Stuart T Nichol Affiliations expand.
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- Research Support, Non-U.S. Gov't
- Ammonium Chloride / pharmacology
- Angiotensin-Converting Enzyme 2
- Antiviral Agents / pharmacology*
- Chlorocebus aethiops
- Chloroquine / pharmacology*
- Fluorescent Antibody Technique, Indirect
- Membrane Glycoproteins / metabolism
- Peptidyl-Dipeptidase A / metabolism
- SARS Virus / drug effects*
- Severe Acute Respiratory Syndrome / drug therapy*
- Severe Acute Respiratory Syndrome / metabolism
- Severe Acute Respiratory Syndrome / prevention & control
- Severe Acute Respiratory Syndrome / virology
- Spike Glycoprotein, Coronavirus
- Vero Cells
- Viral Envelope Proteins / metabolism
- Antiviral Agents
- Membrane Glycoproteins
- Spike Glycoprotein, Coronavirus
- Viral Envelope Proteins
- spike glycoprotein, SARS-CoV
- Ammonium Chloride
- Peptidyl-Dipeptidase A
- Angiotensin-Converting Enzyme 2
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