Protease Inhibitors for the Treatment of SARS-CoV-2

A new coronavirus (SARS-CoV-2) in 2019 was identified as the cause of the first outbreak of pneumonia found in Wuhan, China. Research on the spread, severity, and other functions of the virus is ongoing. Since no vaccines or therapeutic antibodies currently can prevent the infection, targeting specific inhibitors against key proteases involved in virus replication and proliferation is the most effective way to alleviate the epidemic. Based on thousands of clinical drug libraries, scientists have identified three small-molecule drugs with high binding potential to the coronavirus main protease through high-throughput screening, which can be used as candidate drugs for the treatment of SARS-CoV-2 infection.

Therapeutic Potential of Protease Inhibitors for SARS-CoV-2

Since December 2019, a series of unexplained pneumonia cases have occurred in Wuhan, China. Genome sequencing of these patient samples confirmed that the culprit for these infections was beta-coronavirus, which had never been reported before, and was later named SARS-CoV-2. So far, the infection has continued to spread, and more and more cases have been diagnosed in other provinces in China and in other countries in the world, including the United States, which has put tremendous pressure on world public health security.

In order to change this situation, the discovery and clinical application of specific drugs for SARS-CoV-2 are the main goals of related medical research. Genetic test results show that although SARS-CoV-2 is significantly different from SARS-CoV that erupted in Beijing 17 years ago, the sequence identity between them is as high as 79.5%. Further sequence alignment showed that the sequence similarity of major proteases between SARS-CoV-2 and SARS-CoV was as high as 96.1%. This major protease is critical to the life cycle of the virus and can be used as an important detection target for drug development. It is expected that protease inhibitors that can effectively bind will be one of the important means to inhibit the development of disease.

Fig.1 Visualization of 2019-nCoV with Transmission Electron Microscopy. (Zhu, 2020)

• Indinavir (Crixivan): Indinavir is a protease inhibitor that has been used as part of a highly effective antiretroviral therapy for HIV/AIDS. It is a soluble white powder that is taken orally in combination with other antiviral drugs. The drug prevents proteases from functioning normally and has been shown to inhibit coronavirus replication in vitro.

• Nelfinavir (Viracept): Nelfinavir is an antiretroviral drug, which is essentially a protease inhibitor with activity against human immunodeficiency virus type 1 (HIV-1). This drug can block proteases in the virus and inhibit its activity. It is usually used in combination with other antiviral drugs. Previous studies have proven its ability to bind to coronavirus protease, showing its value and potential for clinical application.

• Saquinavir (Fortovase): Saquinavir is an HIV protease inhibitor, a transition state mimetic of phenylalanine-proline (Phe-Pro) peptide bonds. It can competitively inhibit HIV-1 and HIV-2 protease-mediated cleavage of HIV gag and pol polyproteins and prevent post-translational processing of viral polyproteins. In addition, results also found that it has stable binding ability with coronavirus protease and can be used as a candidate for clinical use.

Protease Inhibitor Assay of SARS-CoV-2

To help accelerate the development of anti-SARS-CoV-2 therapeutics, Creative Biolabs can provide protease assays to evaluate inhibitors of SARS-CoV-2 proteases, including:

• Spike-pseudovirus Based Neutralization Assay
• FRET-based assay
• Dose-response titration
• Thermal shift binding assay
• Counter screening assays
• Cellular cytotoxicity test
• Viral yield reduction (VYR) assay
• SARS-CoV-2 CPE assay
• Differential scanning fluorimetry

Creative Biolabs has focused on the development of protease inhibitors for years, we whole-heartedly cooperate with you to accomplish our shared goal. If you have any questions about our SARS-CoV-2 drug discovery services, you can contact us for more details.

Reference

1. Zhu, N.; et al. A novel coronavirus from patients with pneumonia in China, 2019[J]. New England Journal of Medicine. 2020.

For Research Use Only. We do not provide direct services or products for patients.