Anti-Inflammatory Drugs for the Treatment of SARS-CoV-2

The novel coronavirus (SARS-CoV-2) outbreak in Wuhan, China, has rapidly spread and has been reported in multiple countries. As of February 6, 2020, China has confirmed 28,120 cases of SARS-CoV-2 infection. However, for this highly transmissible and lethal coronavirus, there are currently no vaccines or antiviral drugs, so identifying drug treatment options as soon as possible is critical to respond to the SARS-CoV-2 outbreak.

Creative Biolabs has grouped a dedicated strong team who specializes in virology and understands the broad spectrum of coronavirus. Since the SARS outbreak in 2003 and the MERS outbreak in 2012, our professional virologists have been working to develop coronavirus vaccines and antiviral drugs. Over the years, we have accumulated expertise on coronavirus evolution, scientific methodology and continuously updated pathogenic mechanisms. At present, our coronavirus research team focuses on developing anti-inflammatory drugs, which is expected to be the next drug candidate for SARS-CoV-2.

Pathogenesis Mechanism for Coronavirus Infections

Take MERS-CoV as an example. The process of MERS-CoV binding to host cells and virus replication is shown in Figure 1. The type I transmembrane glycoprotein, S protein, is fused to the plasma membrane of the host cell, forming a bilayer membrane vesicle in the host cell, finally releasing the RNA encapsulated in the nucleocapsid, and then performing genome transcription. Viral RNA is replicated and transcribed, followed by 4, 5, and 6 RNA synthesis and translation. The endoplasmic reticulum helps the assembly and packaging of viral particles to form complete double-membrane vesicles. Finally, through exocytosis, MERS-CoV is released from the host cells.

Fig. 1 The life cycle of SARS-CoV and MERS-CoV in host cells. ^1,3

Rationale for Anti-Inflammatory Drugs as potent inhibitors of SARS-CoV-2

Studies have shown that an anti-inflammatory drug - indomethacin (INDO), has been found to possess a potent antiviral activity against coronavirus. INDO does not affect the binding of coronaviruses or entry into host cells, but works by blocking viral RNA synthesis at a cytoprotective dose. It can significantly inhibit virus replication and protect host cells from virus-induced damage. In addition, studies have found that the antiviral activity of INDO is not limited to CCoV, but is also very effective against human SARS-CoV.

ABX464 is another drug candidate with potential triple effect on COVID-19 Treatment: antiviral, anti-inflammatory, and tissue repair. RT-qPCR evaluation found that ABX464 can inhibit the in vitro replication of SARS-CoV-2. ABX464 meets the strategic priorities of the new COVID-19 drugs required by the National Institutes of Health/Institute of Allergy and Infectious Diseases (NIH/NIAID): antiviral, anti-inflammatory, tissue repair, oral, and convenient once-daily administration.

These data suggest that, anti-inflammatory drugs have both anti-inflammatory and antiviral activity, and could be beneficial in SARS-CoV-2 therapy.

Supporting data:

Fig.2 Repression of pan-coronavirus replication in human airway organoids models by Indomethacin. ^2,3

One-Stop Drug Discovery Services

With state-of-art computer-aided drug development platform and advanced bioinformatics technologies, Creative Biolabs is able to provide comprehensive preclinical and clinical development services and solutions for antiviral drugs. From research design, lead optimization to IND enabling, commercialization, Creative Biolabs has the expertise and the only resources you need to help manage our clients anit-SARS-CoV-2 drug development programs.

Fig. 3 Creative Biolabs' preclinical development service process for antiviral drugs.

For more detailed information, please feel free to contact us or directly sent us an inquiry.

References

1. Song, Zhiqi, et al. "From SARS to MERS, thrusting coronaviruses into the spotlight." viruses 11.1 (2019): 59.
2. Wang, Yining, et al. "Combating pan-coronavirus infection by indomethacin through simultaneously inhibiting viral replication and inflammatory response." Iscience 26.9 (2023).
3. Distributed under Open Access license CC BY 4.0, without modification.

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