Indomethacin for the Treatment of SARS-CoV-2

The novel coronavirus (SARS-CoV-2) began in Wuhan, China, has spread rapidly and has now affected 28 countries and regions around the world. As of February 7, 2020, SARS-CoV-2 caused 637 deaths in China. A recent study suggests that the number of deaths will continue to increase. However, there are no known therapies for treating SARS-CoV-2. Therefore, there is an urgent need to develop anti-SARS-CoV-2 drugs.

With years of experience and a broad portfolio of past studies on SARS-CoV and MERS-CoV, Creative Biolabs has cultivated solid expertise in the fields of virology and epidemiology. At present, our virologists have obtained enough evidence to speculate that an anti-inflammatory drug, indomethacin (INDO), has great potential and is expected to be the next drug candidate for SARS-CoV-2.

Introduction of INDO

INDO, also known as indomethacin, is a non-steroidal anti-inflammatory drug (NSAID). It was first approved by the US Food and Drug Administration (FDA) for medical use in 1965. INDO is a non-selective inhibitor of cyclooxygenase (COX) 1 and 2 (enzymes that catalyse the production of prostaglandins) and works by inhibiting the production of prostaglandins.

Other mechanisms of action of INDO include:

• INDO inhibits the movement of polymorphonuclear leukocytes;
• INDO uncouples oxidative phosphorylation in cartilage (and liver) mitochondria;
• INDO has been found to specifically inhibit MRP in mouse and human cells Multidrug resistance protein.

Fig.1 Structure of INDO.

Rationale of INDO as Potent Inhibitors for SARS-CoV-2

CoV replication requires proteolytic treatment of the replicase polyproteins by two viral cysteine proteases, a chymotrypsin-like protease (3CLpro) and a papain-like protease (PLpro). These proteases are important targets for the development of antiviral drugs. INDO, a protease inhibitor, has been identified to possess certain antiviral activity against SARS-CoV in vitro.

Studies also have shown that cyclopentenone prostaglandins have effective antiviral activity against several RNA viruses by interfering with pressure-sensitive cellular signal transduction pathways and transcription factors (including heat shock factor type 1 and nuclear factor kappa B). As mentioned earlier, INDO interferes with prostaglandin synthesis by inhibiting COX synthesis.

Therefore, INDO has the potential to become broad-spectrum antivirals for the treatment of SARS-CoV-2.

The following data further demonstrate that INDO works by blocking viral RNA synthesis at a cytoprotective dose.

End-to-end Drug Discovery Services

Creative Biolabs is committed to providing one-stop small molecule drug development service. Our team strives to bring years of coronavirus therapeutic experience, strategic regulatory guidance and innovative execution to drive your program from preclinical to clinc. Based on our state-of-art computer-aided drug development platform and extensive knowledge in virology, our small drug services range from target identification, structure determination, to biological analysis and synthetic chemistry.

For further details, please don't hesitate to contact us.

Reference

1. Amici, C., et al. Indomethacin has a potent antiviral activity against SARS coronavirus. Antiviral therapy, 2006. 11(8), p.1021.

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